(ALPHA)2(BETA)1 Integrin-Induced Breast Cancer Differentiation
Annual summary 1 Aug 1999-31 Jul 2000
SCRIPPS RESEARCH INST LA JOLLA CA
Pagination or Media Count:
Breast cancer is prone to metastasize to distant organs such as the skeleton. For tumor cells to spread through the blood stream and create distant metastases, they must establish a stable anchorage to the blood vessels and arrest, withstanding the shearing force, before invading the stroma. Several lines of evidence suggest that platelets provide this anchorage. Tumor cells, including breast cancer cells, are known to bind to platelets. In the blood stream, they bind to activated platelets that adhere to the blood vessel walls through bridging molecules such as fibrinogen or von Willebrand factor. Although the molecules on the tumor cells that interact with these bridging molecules have not yet been identified and may vary depending upon the tumor, alpha-IIb-Beta-3 integrin on platelets is responsible for the interaction between platelets and the bridging molecules. Thus, blocking alpha-IIb-Beta-3 function is the common target for preventing the hematogenous metastasis of tumors, including breast cancer. To investigate the ligand binding mechanisms of alpha-IIb-Beta-3, I identified the putative fibrinogen binding site in alpha-IIb, which comprises eight discontinuous short segments. Several amino acid residues within these segments were critical for fibrinogen binding. These findings will be the basis for developing antimetastasis therapeutics for breast cancer.
- Medicine and Medical Research