Bone Abstracts

Metastases to the bone are the incurable final outcomes of cancer, reducing both length and quality of life in an aggressive way. Despite the discoveries of many factors involved, no cure has been found. Metastatic outgrow starts in interaction with the bone micro-environment. The first attachment in bone is with the osteoblasts lining the endosteal surface. Our aim is to study the role of the osteoblasts in metastatic tumor spread and growth.

We used an in vitro differentiating pre-osteoblast cell line (SV-HFO) and two metastatic prostate cell lines, a bone (PC-3) and a non-bone (lymph) metastasis (LNCaP). This co-culture system enabled us to study mutual effects from metastatic cancer cells and osteoblasts at the same time. To distinguish tumor cells from osteoblasts, stably GFP expressing PC-3 and LNCaP cells were generated.

SV-HFO osteoblasts differentiate in culture in a 3-weeks period from early undifferentiated cells into differentiated osteoblasts with a mineralized extracellular matrix. When co-cultures with metastatic prostate cancer cells were performed specifically at the undifferentiated or differentiated osteoblasts, undifferentiated osteoblasts stimulated cell growth of PC-3 and LNCaP while differentiated osteoblasts inhibited cell growth of PC-3 and LNCaP.

When co-cultures were started at the undifferentiated osteoblasts and continued for 3 weeks, PC-3 cell growth was stimulated while LNCaP cell growth was inhibited at the end of the culture. This was caused by the fact that only PC-3 cells inhibited osteoblast differentiation and kept the osteoblasts in an undifferentiated stage, while LNCaP had no effect on osteoblast differentiation.

Conclusion: Our study provides evidence that bone metastatic cancer cells can survive and grow in bone by impairing osteoblast differentiation and keeping them in a tumor cell growth stimulatory stage while non-bone metastatic cancer cells are unable to do so. This may form an important basis for cancer therapies based on bone metabolism.