SPECIFIC ADHESION OF PROSTATE AND BREAST CANCER CELLS TO BONE-DERIVED MESENCHYMAL STEM CELLS AND THEIR OSTEOBLASTIC LINEAGE DIFFERENTIATION STAGE

Abstract

The propensity of specific organs to harbor metastatic tumors is maintained by reciprocal interactions between cancer cells and the organ’s microenvironment. Bone is the third most common site of metastasis for several solid tumors. Prostate and breast cancer cells show high affinity for bone colonization. Tumor cells extravasate from systemic circulation by adhering and traversing adjacent vascular endothelial cells. Successfully extravasated cancer metastatic cells interact with bone-lining cells that include several cell types at different differentiation states. Understanding of the molecular and cellular mechanisms that govern breast and prostate cancer cells homing to bone is an important field of research in cancer therapy that might yield novel potential targets. The overall aim of this study is to ascertain whether bone metastatic cancer cells adhere to a specific class of cells within bone tissues. We will evaluate adhesion of prostate and breast cancer cells to Mesenchymal Stem Cells (MSC) and to MSCs induced to differentiate into osteoblastic lineage at different time points. Exploring specific potential cancer cells molecules involved in initiating and maintaining adhesion to the bones is an essential step to formulate novel modalities for therapeutic intervention. ¬We will establish an in vitro model of co-cultured MSC/Osteoblasts-cancer cells (Breast MDA 231 and Prostate PC 3). The system will be evaluated at different time points representing partially differentiated osteoblasts and presumably fully differentiated osteoblasts. MSCs differentiation, gene expression, protein expression and cellular localization assays will be performed, with the aim of determining the state with the highest cell-cell adhesion affinity and evaluating cancer cells-stem cells to osteoblasts interactions. The cell type with the highest adhesion affinity to cancer cells will be used to expand the co-culture system and establish more complex in vitro model with endothelial cells-cancer cells (Breast MDA231 and Prostate PC3) cultured on extracted bone extracellular matrix. This system, which closely mimics the bone microenvironment, will facilitate the study of cancer cell extravasation to bone and to unravel the cellular and molecular events in organ preference of metastasis.