Our researchers demonstrated that components of the tumor microenvironment influence the response of hematopoietic cell lines to chemotherapeutics and could contribute to de novo resistance. It is propose that a viable strategy for enhancing the efficacy of currently used cytotoxics is to identify targets which contribute to de novo drug resistance thereby increasing the efficacy and success of initial therapy intervention and decreasing relapse rates. It was shown that adhesion of leukemia and multiple myeloma cell lines to the extracellular matrix component, fibronectin (FN) via β1 integrin, is sufficient to inhibit drug-induced apoptosis.
HYD1 is a peptide that binds and inhibits β1 integrin-mediated adhesion. Recently it has been demonstrated that HYD1 potentiates melphalan induced cell death. Allowing direct contact between tumor cells and the bone marrow stroma cell line HS-5 is sufficient to confer a multi-drug resistant phenotype. Our researchers demonstrated that HYD1 potentiates melphalan induced cell death in multiple myeloma cell lines that are co-cultured with the HS-5 cell line. HYD1 will be shown to increase the efficacy of drug treatment in an in vivo model.
Influence of BMS cells on CAM-DR of the tumor cell and acquisition of acquired drug resistance