Prostate cancer commonly metastasizes to bones. Metastasis formation is a multistep process that includes interactions of cancer cells with endothelium of organ of metastasis residency. Interference with any stage of metastatic process including cancer cells-endothelium interactions may be helpful in the fight against metastatic disease. To inhibit these interactions peptide ligands specific to intercellular adhesion molecules can be used. It was suggested earlier that prostate cancer cells preferentially binds to bone marrow endothelial cells. Identification of the set of peptide inhibitors for attachment of prostate cancer cells to human bone marrow endothelium is proposed. Peptide ligands that bind to the molecules expressed on the surface of several types of prostate cancer cells will be determined through phage display peptide libraries. Combination of the peptides that inhibit adhesion of prostate cancer cells to bone marrow endothelial cells most effectively will be selected among the cancer cell-specific binders. We believe that obtained information will be valuable for the design of the lead compound for creation of antiadhesion reagent. The developed compound may be used as a model for the design of pharmacological anti-metastatic agent after examination on in vivo models.
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| Romanov, Victor I; Whyard, Terry; Adler, Howard L et al. (2004) Prostate cancer cell adhesion to bone marrow endothelium: the role of prostate-specific antigen. Cancer Res 64:2083-9 |
