Cancer and bone: basic, translational and clinical

ba0005p98 | Cancer and bone: basic, translational and clinical | ECTS2016

The cigarette smoking condensates effects on microRNA regulation in calcified of bladder carcinogenesis and progression

Zeng Bao Rung , Zeng Pao-Rung , Yu Cheng-Ping

Backgrounds: Bladder cancer is the most common malignancy and also highest mortality of the urinary tract cancer. Urothelial cell carcinoma (UCC) is the most histopathological subtype of bladder cancer. Epidemiological studies have indicated that bladder cancer risk for cigarette smoking is more than twice than never smoking and that current cigarette smoking triples bladder cancer risk relative to never smoking. Cigarette smoking after bladder cancer diagnosis decreases cance...

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ba0005p99 | Cancer and bone: basic, translational and clinical | ECTS2016

DNA-methylation status affects prognostic markers of bone metastasis from breast carcinoma

Maroni Paola , Bendinelli Paola , Matteucci Emanuela , Desiderio Maria Alfonsina

Metastasis to bone is the leading cause of death for breast carcinoma, and much focus in the biology and therapy relays on epigenetic alterations. Since DNA-methyltransferase blockade counteracts tumour growth, we utilized 5-aza-2′-deoxycytidine (dAza) to clarify whether molecular events undergoing epigenetic control were critical for bone metastatization. Here, we studied Secreted-Protein Acidic and Rich in Cysteine (SPARC), matricellular glycoprotein associated with bo...

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ba0005p100 | Cancer and bone: basic, translational and clinical | ECTS2016

The clinicopathological implication of GNAS in ewing sarcoma

Noh Byeong-Joo , Sung Ji-Youn , Kim Youn Wha , Araujo Eduardo Santini , Kalil Ricardo Karam , Jung Woon-Won , Kim Hyun-Sook , Park Yong-Koo

The objective of our study is to determine whether GNAS expression correlates with pathognomonic signs by analyzing mutations, methylation status, and G-protein α subunit (Gsα) expression of GNAS (guanine nucleotide binding protein/α stimulating) gene in Ewing Sarcoma (ES).Formalin-fixed paraffin-embedded (FFPE) tissue samples from 77 patients with primary ES were obtained in Korea, Argentina, and Brazil, and w...

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ba0005p101 | Cancer and bone: basic, translational and clinical | ECTS2016

Bisphosphonates and the risk of breast cancer in osteoporotic women: a population-based study

Rouach Vanessa , Goldshtein Inbal , Chodick Gabriel , Catane Rafael , Stern Naftali , Cohen Daniel

Background: Bisphosphonates (BP) are widely used in osteoporosis treatment. By inhibiting the mevalonate pathway, bisphosphonates may affect cell function and survival, including the viability of tumor cells. Recently, a protective effect of bisphosphonates on breast cancer risk has been suggested by several studies, which were unable to exclude the possibility of a confounder effect due to low cumulative exposure to estrogen in osteoporotic women vs controls.<p class="abs...

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ba0005p102 | Cancer and bone: basic, translational and clinical | ECTS2016

Inhibition of mTOR signaling by everolimus has concurrent anti-tumor and bone-protective effects in murine osteolytic cancer models

Browne Andrew , Kubasch Marie Luise , Gobel Andy , Hadji Peyman , Chen David , Rauner Martina , Rachner Tilman , Hofbauer Lorenz

Clinical data suggest that the mTOR inhibitor everolimus may have bone protective effects in addition to its anti-tumor effects in women with ER+/HER2− metastatic breast cancer receiving hormone-ablative therapies. Based on these findings, we tested the hypothesis, whether everolimus exerts concurrent anti-tumor effects while protecting the skeleton in murine models. Thus, we assessed bone metabolism and anti-tumor effects in osteolytic cancer models upon exposure to eve...

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ba0005p103 | Cancer and bone: basic, translational and clinical | ECTS2016

Conventional and Pagetic Giant Cell Tumor of bone: distinct clinical features are defined by different genetic background and histological appearance

Divisato Giuseppina , di Carlo Federica Scotto , Esposito Teresa , Pazzaglia Laura , Benassi Maria Serena , Merlotti Daniela , Rendina Domenico , Gennari Luigi , Gianfrancesco Fernando

Conventional Giant Cell Tumor of Bone (GCT) is an aggressive bone tumor characterized by malignant mesenchymal stromal cells, responsible for its unusually high population of multinucleated osteoclast-like giant cells. GCT could arise in bones affected by Pagets disease of bone (GCT/PDB) with a different clinical profile regarding the age-onset of the neoplasm (30 years vs 50 years) and the skeletal localization (appendicular skeleton vs cranio-facial bones), let hyphote...

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ba0005p104 | Cancer and bone: basic, translational and clinical | ECTS2016

Long-term effect of aromatase inhibitor on bone mineral density, trabecular bone score, and hip geometry in postmenopausal women with primary breast cancer

Hong A Ram , Kim Jung Hee , Lee Kyung-Hun , Kim Tae Yong , Im Seock-Ah , Kim Tae-You , Moon Hyung-Gon , Han Wonshik , Noh Dong-Young , Kim Sang Wan , Shin Chan Soo

Background: Aromatase inhibitors (AIs) increase the risk of fracture in patients with breast cancer. Therefore, we aimed to evaluate the long-term effects of AIs on bone health in postmenopausal women with primary breast cancer.Patients and methods: We performed a retrospective longitudinal observational study in patients with breast cancer who were treated by AIs for &gE;3 years (baseline T-score >2.5). Patients with previous anti-osteoporosis...

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ba0005p105 | Cancer and bone: basic, translational and clinical | ECTS2016

Effects of the female hormone inhibin-A in vivo: potential contribution to the antitumour effect of Zoledronic acid

Wilson Caroline , Nutter Faith , Brown Hannah , Coleman Robert , Holen Ingunn

Background: Breast cancer clinical trials have shown an enhanced anti-tumour activity of bone-targeted agents in postmenopausal patients. We have reported that zoledronic acid (ZOL) decreases serum levels of the tumour promoter follistatin in postmenopausal women and also inhibits expression of follistatin by breast tumour cells both in vitro and in vivo. We hypothesised that inhibin-A (InA) and ZOL may be altering bone levels of follistatin and its bound tum...

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ba0005p106 | Cancer and bone: basic, translational and clinical | ECTS2016

The Rho GTPases RhoA and CDC42 mediate apoptosis by a combination of statins and zoledronic acid in human bone-seeking breast cancer cells

Gobel Andy , Thiele Stefanie , Browne Andrew J , Rauner Martina , Hofbauer Lorenz C , Rachner Tilman D

Breast cancer is the most frequent malignancy in women and frequently results in osteolytic bone metastases. Amino-bisphosphonates are a standard bone protective therapy and, similarly to statins, inhibit the mevalonate pathway that is crucial for posttranslational protein modifications (farnesylation and geranylation). Direct anti-tumor effects of amino-bisphosphonates and statins have been suggested but high concentrations are necessary to achieve meaningful effects. Our stu...

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ba0005p107 | Cancer and bone: basic, translational and clinical | ECTS2016

Biological effects of Cabozantinib on bone microenvironment

Pantano Francesco , Fioramonti Marco , Iuliani Michele , Ribelli Giulia , Vincenzi Bruno , Tonini Giuseppe , Santini Daniele

Background: Cabozantinib (CBZ) is a receptor tyrosine kinase inhibitor with activity against MET, VEGFR2, FLT3, c-KIT, and RET. Pre-clinical studies in models of prostate cancer bone metastasis demonstrated that CBZ treatment induced both a suppression of tumour growth and an alteration in bone remodelling, suggesting that both tumour and bone microenvironment represented potential CBZ targets. This is the first study exploring the potential direct activity of CBZ in bone usin...

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ba0005p108 | Cancer and bone: basic, translational and clinical | ECTS2016

Clinical and experimental evidence suggest a protective effect of Paget’s disease of bone against skeletal metastasization from solid tumors

Merlotti Daniela , Rucci Nadia , Rendina Domenico , Bianciardi Simone , Evangelista Isabella Anna , Ucci Argia , Rotatori Stefano , Sebastiani Guido , Dotta Francesco , Cenci Simone , Strazzullo Pasquale , Nuti Ranuccio , Teti Anna , Gennari Luigi

Pagets disease of bone (PDB) is a common disorder of bone metabolism characterized by focal areas of excessive and rapid bone resorption and formation, leading to bone pain, deformity and fractures. Despite the well documented increase in the risk of primary bone tumors due to neoplastic degeneration of pagetic tissue, a large retrospective analysis suggested that patients with prostate cancer and PDB have delayed time to bone metastases and improved overall survival tha...

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ba0005p109 | Cancer and bone: basic, translational and clinical | ECTS2016

Antiproliferative properties of oleuropein in human osteosarcoma cells

Moran Jose M , Leal-Hernandez Olga , Canal-Macias Maria L , Lavado-Garcia Jesus M , Roncero-Martin Raul , Aliaga Ignacio , Pedrera-Zamorano Juan D

Background: Cancer is one of the leading causes of death worldwide. Natural products have been regarded as important sources of potential chemotherapeutic agents. In this study, we evaluated the antiproliferative activity of oleuropein, an olive oil compound traditionally found in the Mediterranean diet.Design and Methods: The antiproliferative activity on two human osteosarcoma cell lines (MG-63 and Saos2) was evaluated in vitro using the MTT c...

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ba0005p110 | Cancer and bone: basic, translational and clinical | ECTS2016

Role of the receptors FZD8 and RYK in mediating the anti-tumor effects of WNT5A on prostate cancer cells

Thiele Stefanie , Gobel Andy , Hippauf Sandra , Rachner Tilman , Rauner Martina , Hofbauer Lorenz C

Wnt proteins and their cognate receptors play a significant role in malignant diseases, in particular in prostate cancer (PCa). We previously showed that WNT5A inhibits PCa cell proliferation and induces apoptosis in vitro, leading to reduced PCa growth in vivo. However, the involved receptors remain unknown. Here, we determine the role of two Wnt receptors (FZD8, RYK) and their influence on the WNT5A-induced effects on PCa cells.The ex...

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ba0005p111 | Cancer and bone: basic, translational and clinical | ECTS2016

Changes in monocyte and NK-like cell subpopulations in the peripheral blood of patients treated with zolendronic acid

Kyrgidis Athanassios , Yavropoulou Maria , Lagoudaki Rosa , Andreadou Anna , Andreadis Charalambos , Yovos John , Kouvelas Dimitrios

: Osteonecrosis of the jaws (ONJ) is a relatively new adverse effect associated with bisphosphonate therapy, but no causal association has been established. By definition, a patient is considered to suffer from ONJ if he has current or previous treatment with a bisphosphonate, exposed bone in the maxillofacial region that has persisted for more than 8 weeks and no history of radiation therapy to the jaws. It has been proposed that ONJ could be linked with impaired topical immu...

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ba0005p112 | Cancer and bone: basic, translational and clinical | ECTS2016

Myeloid-derived suppressor cells (MDSC) mediate the positive feedback loop of prostate tumor-bone interactions

Park Serk in

Advanced-stage prostate and breast cancer patients commonly develop bone metastases, accounting for significant clinical problems such as pain, fracture, immobility and death. Bone is comprised of diverse cell types that are potentially involved in metastatic progression. However, how cancer cells interact with these cells within the bone microenvironment to support their expansion and activity remains unclear. Recent data from our laboratory highlighted a novel feed-forward m...

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ba0005p113 | Cancer and bone: basic, translational and clinical | ECTS2016

Dendritic glycopolymers as efficient drug delivery systems for retarded release of bortezomib from calcium phosphate cements

Mamitzsch Bettina , Striegler Christin , Schumacher Matthias , Gelinsky Michael , Muller Martin , Seckinger Anja , Voit Brigitte , Appelhans Dietmar

Calcium phosphate cements (CPC) are used as bone graft substitute, e.g. in the treatment of lytic bone lesions in multiple myeloma. CPC provide crucial advantages, such as osteoconductivity, biodegradability and the potential drug loading. Though, it lacks retarded drug release for short-/long-term treatment due to the free diffusion of small molecules through the micropores in the CPC.Thus we present dendritic glycopolymers (DG) consisting of poly(ethyl...

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ba0005p114 | Cancer and bone: basic, translational and clinical | ECTS2016

Increased zinc accumulation in mineralized osteosarcoma tissue

Rauwolf Mirjam , Pemmer Bernhard , Roschger Andreas , Turyanskaya Anna , Simon Rolf , Lang S. , Puchner S E , Windhager Reinhard , Klaushofer Klaus , Wobrauschek Peter , Hofstaetter Jochen G , Roschger Paul , Streli Christina

Abnormal tissue levels of certain trace elements such as Zinc (Zn) were reported in various types of cancer. Little is known about the role of Zn in osteosarcoma.Using confocal synchrotron radiation micro X-ray fluorescence analysis, we characterized the spatial distribution of Zn in high-grade (G3) sclerosing osteosarcoma of nine patients (4 f/5 m; 7 knee/1 humerus/1 femur) following chemotherapy and wide surgical resection. The study was done in accord...

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ba0005p115 | Cancer and bone: basic, translational and clinical | ECTS2016

Polycystin-1 is involved in osteosarcoma pathobiology

Adamopoulos Christos , Gargalionis Antonios N. , Malakou Lina , Katsianou Maira , Grivaki Christofora , Agrogiannis Georgios , Korkolopoulou Penelope , Piperi Christina , Basdra Efthimia K. , Papavasiliou Athanasios G.

Osteosarcoma is the most common primary bone-derived tumor. However, the pathogenic molecular mechanism(s) underpinning osteosarcoma development and metastasis remain elusive. The polycystins PC1 (polycystin-1; encoded by PKD1) and PC2 (polycystin-2) are central players in mechanotransduction, a process that can influence all steps of the invasion/metastasis cascade. Recent studies from our laboratory provided, for the first time, a direct link between mechanosensing polycysti...

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ba0005p116 | Cancer and bone: basic, translational and clinical | ECTS2016

Signaling network of mirnas regulating bone metastasis in lung cancer

Zhao Qian , Lang Jiangli , Xie Ying , Chen Xiang , Tian Li , Yu Xijie

We found that miR-335 is reduced in SBC-5, a human lung cancer (LC) derived cell lines inducing osteoclast formation by expressing RANKL; reviving miR-335 expression in SBC-5 results in decrease of its proliferation, invasion, migration and clone formation in vitro; reviving miR-335 expression in LC model leads to reduction of bone metastasis (BM) in vivo. It was confirmed that miR-335, inhibiting the formation and activity of osteoclasts and reducing the pro...

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ba0005p117 | Cancer and bone: basic, translational and clinical | ECTS2016

Contribution of multiple myeloma-derived exosomes to bone disease

Raimondi Lavinia , De Luca Angela , Carina Valeria , Agnese Valentina , Fontana Simona , Monteleone Francesca , Saieva Laura , Alessandro Riccardo , Giavaresi Gianluca

Bone disease is the most frequent complication in multiple myeloma (MM) resulting in pain, bone fractures, spinal cord compression and hypercalcemia. Within the bone marrow microenvironment (BMM), MM cells interact with bone cells to enhance bone resorption activity and compromise new bone formation mechanism; in turn, BMM provides a survival and drug resistance framework by interaction of MM cells with bone marrow components. Exosomes are important mediators of crosstalk betw...

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ba0005p118 | Cancer and bone: basic, translational and clinical | ECTS2016

Menin is a tumor suppressor in bone -- a novel benign jaw tumor mouse model

Lee Sooyeon , Liu Peng , Tschaffon Miriam , Tasdogan Alpaslan , Wittig Rainer , Frappart Lucien , Knoll Jeanette , Bertolino Philippe , Zhang Chang , Tuckermann Jan

Benign jaw tumors including ossifying fibroma (OF) can be often incidentally diagnosed due to their slow-growing and painless characteristics. In cases of massive growing jaw tumors, it can result in deformity of teeth, infection and intracranial complications. Depending on the location of tumor lesion, it may not completely resected and recur after the primary operation, which may require subsequent operations.Molecular mechanisms and the etiology of th...

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ba0005p119 | Cancer and bone: basic, translational and clinical | ECTS2016

Abstract unavailable....

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ba0005p120 | Cancer and bone: basic, translational and clinical | ECTS2016

The role of acidic microenvironment in the context of osteolytic carcinomas

Di Pompo Gemma , Lemma Silvia , Canti Lorenzo , Gillies Robert , Baldini Nicola , Avnet Sofia

The microenvironment of osteolytic metastases includes carcinoma cells derived from the primary lesion as well as bone-forming and bone-resorbing cells, namely osteoblasts (OB) and osteoclasts (OC). At this site, both the high glycolysis of cancer cells, and the bone resorption process result in a very acidic milieu. This, in turn, induces the surrounding stroma and OB to secrete pro-inflammatory cytokines and growth factors that promote tumorigenesis and cancer-associated ost...

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ba0005p121 | Cancer and bone: basic, translational and clinical | ECTS2016

MCT1 as a novel target for the treatment of osteolytic bone metastases

Avnet Sofia , Lemma Silvia , Di Pompo Gemma , Sboarina Martina , Porporato Paolo , Perez-Escuredo Jhudit , Sonveaux Pierre , Baldini Nicola

Bone metastasis (BM) is a dismal complication of cancer, occurring frequently in patients with advanced breast carcinoma. During metastatic progression, carcinoma cells harness osteoclast (OC) activity, promoting osteolysis. To adapt to hypoxia and/or to support proliferation, carcinoma cells adopt primarily glycolysis for energy production, therefore releasing lactic acid in the microenvironment through monocarboxylate transporter 4 (MCT4). Stressed by tumor cells, osteoblast...

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ba0005p122 | Cancer and bone: basic, translational and clinical | ECTS2016

Acetate metabolism in Multiple Myeloma identifies ¹¹C-Acetate PET as a novel strategy to image bone disease and response to treatment in preclinical models

Fontana Francesca , Ge Xia , Su Xinming , Xiang Jingyu , Cenci Simone , Civitelli Roberto , Shoghi Kooresh , Akers Walter , D'Avignon Andre , Shokeen Monica , Weilbaecher Katherine

Multiple Myeloma (MM) is a malignancy of Plasma Cells (PC), characterized by severe osteolytic lesions but poor 99Tc-MDP uptake in bone scans due to osteoblast inhibition. We hypothesized that high demands for membrane biosynthesis in tumour PC would enhance monocarboxylic acid anabolism and uptake, which could be exploited for treatment and molecular imaging. Here, we tested the efficacy of clinically available 11C-Acetate PET to detect myeloma and quant...

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ba0005p123 | Cancer and bone: basic, translational and clinical | ECTS2016

The SRC kinase inhibitor saracatinib limits the development of osteolytic bone disease in multiple myeloma

Heusschen Roy , Muller Josephine , Binsfeld Marilene , Plougonven Erwan , Mahli Nadia , Carmeliet Geert , Leonard Angelique , Cohen-Solal Martine , Vanderkerken Karin , Beguin Yves , Menu Eline , Caers Jo

Destructive bone lesions due to osteolytic bone disease (OBD) are a major cause of morbidity and mortality in multiple myeloma (MM) patients and the development of new therapeutic strategies is of great interest. In this study, we assessed the effect of SRC inhibition with saracatinib (AZD0530, AstraZeneca) on the development of MM and its associated OBD. We first determined SRC family kinase expression in the MM microenvironment and found that myeloma cells express SRC at low...

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ba0005p124 | Cancer and bone: basic, translational and clinical | ECTS2016

Gene expression of P2 receptors in mitotically quiescent, prostate cancer bone metastasis initiating cells

Amin Zarkesh Sayyed , Docherty Freyja , Eaton Colby , Wang Ning

Rationale and hypothesis: In ~70% of advanced prostate cancer (PCa) patients, incurable bone metastases are a significant cause of morbidity and mortality. It has been shown that in models of PCa, bone metastases are initiated by a minor subset (<1% of total cell population) that are mitotically quiescent and which have undergone epithelial to mesenchymal transition (EMT). Recent studies have shown that various P2 receptors regulate invasiveness/EMT in different types of c...

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ba0005p125 | Cancer and bone: basic, translational and clinical | ECTS2016

Host-derived MMP-13 promotes Multiple Myeloma skeletal colonization

Shay Gemma , Lo Chen-Hao , Hazlehurst Lori , Lynch Conor

A hallmark of Multiple Myeloma is skeletal colonization resulting in painful osteolytic lesions. Matrix metalloproteinase-13 (MMP-13) is a type-1 collagenase largely expressed by mesenchymal stromal cell (MSCs) in the bone tissue. In agreement, immunohistochemical staining of human myeloma biopsies demonstrated the localization of MMP-13 to the stromal compartment with expression in a subset of myeloma cells. This observation was further supported by studies showing that co-cu...

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ba0005p126 | Cancer and bone: basic, translational and clinical | ECTS2016

Interactions between cancer and osteocytes in bone

Keller Evan

Cross talk between tumour cells and the host microenvironment plays a critical role in tumour progression. There have been multiple studies that have highlighted the importance of proteins secreted by tumour cells that then act on the tumour microenvironment and by proteins secreted by the host microenvironment that promote tumour progression at the metastatic niche. However, little is known regarding the role of physical forces on tumour progression.Bon...

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ba0005p127 | Cancer and bone: basic, translational and clinical | ECTS2016

LIGHT promotes osteolytic bone metastases in NSCLC patients

Brunetti Giacomina , Belisario Dimas Carolina , Alliod Valentina , Buffoni Lucio , Colucci Silvia , Grano Maria , Ferracini Riccardo , Roato Ilaria

LIGHT is a TNF superfamily member, expressed by activated T cells. It is involved in erosive bone disease, such as rheumatoid arthritis where it stimulates osteoclastogenesis. In multiple myeloma, LIGHT promotes osteolysis by increasing osteoclastogenesis and inhibiting osteoblastogenesis. We investigated whether LIGHT has a role in the osteolytic bone metastatic process induced by non small cell lung cancer (NSCLC), which is a tumor with a marked osteotropism. We analysed by ...

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ba0005p128 | Cancer and bone: basic, translational and clinical | ECTS2016

The pharmacological profile of a novel highly potent bisphosphonate, OX14 (1-fluoro-2-(imidazo-[1,2 alpha]pyridin-3-yl)ethyl-bisphosphonate), with reduced bone affinity, which is as effective as zoledronate in the treatment of myeloma bone disease in JJN3-NOD/SCID-γ mice

Lawson Michelle , Chantry Andrew , Paton-Hough Julia , Evans Holly , Lath Darren , Tsoumpra Maria , Lundy Mark , Dobson Roy , Quijano Michael , Kwaasi Aaron , Dunford James , Duan Xuchen , Triffit James , Mazur Adam , Jeans Gwyn , Russell Graham , Ebetino Hal

Bisphosphonates are used in the treatment of a variety of diseases with skeletal complications. With the development of more potent compounds, there is the potential for further improvement. One concept is to use compounds with a reduced affinity for bone, reducing their long-term retention and possible adverse events, as well as potentially enhancing their non-skeletal benefits. We hypothesise that a highly potent bisphosphonate with low bone affinity, known as OX14, will be ...

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ba0005p129 | Cancer and bone: basic, translational and clinical | ECTS2016

Vertebral fractures among breast cancer survivors in China

Hsieh Evelyn , Wang Qin , Zhang Renzhi , Niu Xin , Li Jing , Zhou Chunwu , Qiao Youlin , Xia Weibo , Fraenkel Liana , Insogna Karl , Smith Jennifer , Zhang Pin

Background: Women with breast cancer (BC) are at high risk for fracture due to the deleterious impact of BC therapies on bone. In China, BC survival is improving as screening and treatment programs expand, however no guidelines exist to prevent BC treatment-induced bone loss. We sought to evaluate the scope of this problem among BC survivors receiving care at a large cancer referral hospital in China.Methods: Women were invited to participate in this cro...

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ba0005p130 | Cancer and bone: basic, translational and clinical | ECTS2016

Uptake of different nitrogen containing bisphosphonate formulations by breast cancer cells

Zlatev Hristo , Auriola Seppo , Monkkonen Jukka , Maatta Jorma

Nitrogen-containing bisphosphonates (N-BPs) are used to treat osteolytic bone metastases. N-BPs have been previously shown to enter macrophages via macropinocytosis, but the mechanisms how they are taken up by breast cancer cells are so far incompletely known. In breast cancer primary tumours N-BPs have been shown, by other researchers, to be bound to micro-calcifications present in the tumour stroma. In our study we have characterized how different N-BP formulations, free, ca...

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ba0005p131 | Cancer and bone: basic, translational and clinical | ECTS2016

MicroRNA-30 family regulates bone tropism and osteomimicry in human breast cancer cells

Martine Croset , Francesco Pantano , Casina Kan , Edith Bonnelye , Catherine Alix-Panabieres , Charles Lecellier , Saw-See Hong , Kai Bartkowiak , Klaus Pantel , Philippe Clezardin

Breast cancer cells that escape primary tumors disseminate to bone with high affinity at late-stage disease. Circulating breast tumor cells that invade the bone marrow (BM) express sets of deregulated genes and/or microRNAs (miRNAs) that facilitate their bone tropism and enhance engraftment of disseminated tumor cell (DTC) in BM which may subsequently induce osteolytic lesions. MiRNA transcriptomic profiling of the human breast cancer DTC cell line, BC-M1, and of the osteotrop...

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ba0005p132 | Cancer and bone: basic, translational and clinical | ECTS2016

Osteoblast-derived factors increased metastatic potential in human prostate cancer cells

Karlsson Terese , Sundar Reshma , Widmark Anders , Landstrom Marene , Persson Emma

In prostate cancer TGFβ promotes invasion and metastatic potential. One well-known cellular source of TGFβ in the bone metastatic site is the bone-forming osteoblasts. Here we have studied the effects by human osteoblast-derived factors on metastatic potential in cells from the human bone metastatic prostate cancer cell line PC-3U and the primary prostate cancer cell line 22Rv1. Osteoblast-derived factors resulted in a morphological effect with an increase of long ce...

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ba0005p133 | Cancer and bone: basic, translational and clinical | ECTS2016

Novel evidence that ApoA-1 deficiency facilitates HSC mobilization and differentiation and halts HSC quiescence and self-renewal in mice

Mastora Ioulia , Papachristou Nicholaos , Blair Harry , Kalyvioti Elena , Syggelos Spyros , Karavia Eleni , Kypreos Kyriakos , Papachristou Dionysios

Recent evidence suggests that osteoblastic bone marrow niche is vital for the maintenance and self-renewal of hematopoietic stem cells (HSC). It has been recently proposed that cholesterol efflux pathways participate in HSC mobilization and that cholesterol-sensing pathways control the proliferation of HSC progenitors. Moreover, we have recently documented that HDL perturbations result in impaired osteoblastic function in mice. In the present study, we aimed at investigating t...

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ba0005p134 | Cancer and bone: basic, translational and clinical | ECTS2016

Encapsulation of Gli-inhibitors blocks tumor invasion into the bone

Vanderburgh Joseph , Cannonier Shellese , Kwakwa Kristin , Merkel Alyssa , Werfel Thomas , Duvall Craig , Guelcher Scott , Sterling Julie

It is well established that tumor expression of Gli2, a Hedgehog family transcription factor, contributes to tumor-induced bone disease. Our previous studies investigating genetic inhibition of Gli2 expression in tumor cells have shown promise for the development of therapeutics. While many groups have focused on developing upstream Hedgehog inhibitors for soft-tissue tumors that aberrantly express Gli proteins, we have previously demonstrated that the expression of Gli2 in tu...

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43rd Annual European Calcified Tissue Society Congress

BiosciAbstracts