Bone Abstracts

The concept of the vicious cycle of bone metastases emphasizes the cross-talk between osteoclasts, osteoblasts and tumor cells, but the role of bone marrow stromal cells (BMSCs) is not well delineated. BMSCs comprise of a fibroblast-like cell population which adhere to culture flask and have an ability to differentiate into osteoblasts, adipocytes and chondrocytes. They express a panel of cell surface antigens which includes CD105, CD73, CD90, CD106, and CD146. In this study we aimed to further characterize this heterogeneous cell population with a specific focus on the role of CD146 positive cells.

Bone marrow cells from the tibia of C57BL/6 mice were flushed and treated with red blood cell lysing solution to obtain a population of mononuclear cells. Cells were cultured on coverslips for 18–30 days and stained for osteogenic and fibroblastic markers. Staining for CD146 was also performed on tibia harboring bone metastases. Staining was performed on untreated mice or those treated with alendronate.

The majority of cells expressed abundant amounts of α-SMA and COL1A1 while CD146, FAPα and FSP-1 were expressed at low levels only by a sub-population of cells. No Desmin staining was observed. To determine a potential role of CD146 positive cells in vivo, a mouse model of breast cancer bone metastases was utilized. The presence of CD146 positive cells was examined by immunohistochemistry. Mice treated with alendronate had reduced tumor size compared to untreated controls. Surprisingly, there was a 60% increase in the presence of CD146 positive cells in the tumor region with alendronate treatment (P<0.05).

The data support the premises that BMSCs are inherent osteoprogenitor cells. The increased abundance of CD146 positive sub-population with alendronate treatment indicates that this cell type has a potential role in inhibiting tumor growth. Further evaluation of the role of CD146 in bone metastases is required.