Prostate cancer bone metastasis is a major clinical problem and is commonly associated with intractable pain and spinal cord compression. Nearly 100% of men who die of prostate cancer have bone metastases. The interactions involved in organ-specific metastasis are not well characterized. Adhesion of cancer cells to cell adhesion molecules present on a target organ's microvascular endothelium, in part, regulates this process. The first cell a cancer cell will encounter as it exits the blood circulation and enters a preferred organ is the endothelial cell in the organ's microvessel. Previous studies suggest that prostate cancer metastasis to bone is mediated, in part, by preferential adhesion to bone marrow endothelium. Therefore, it is critical to identify CAMs expressed on the bone marrow endothelium that mediate prostate cancer cell adhesion. Preliminary data demonstrate: A) The preferential binding of prostate cancer cells to human bone marrow endothelial (HBME) cells as compared to other endothelial cells. B) The isolation of a novel protein expressed in HBME cells by phage display using prostate cancer cells (PC-3). This protein is tentatively named Expressed in HBME cells (EIHC). C) The determination of the 3' end for EIHC by RACE. The phage expressing EIHC cDNA was selected because it interacted with CAMs on the surface of PC-3 cell monolayer. Therefore, the hypothesis of this grant is that EIHC, in part, mediates preferential binding between prostate cancer cells and human bone marrow endothelial cells. To investigate our hypothesis, we have developed the following Specific Aims: 1) Sequence and analyze the complete EIHC gene. 2) Determine the role EIHC plays in the preferential adhesion of prostate cancer cells to the HBME cell line. 3) Determine the expression of EIHC in the HBME cell line and other selected cell lines. A better understanding of the role that bone endothelium plays in PC metastasis to bone is important for defining a therapeutic strategy to block the development of these metastases in prostate cancer patients.
| Stewart, Delisha A; Cooper, Carlton R; Sikes, Robert A (2004) Changes in extracellular matrix (ECM) and ECM-associated proteins in the metastatic progression of prostate cancer. Reprod Biol Endocrinol 2:2 |
