YIGSR, a synthetic laminin peptide, inhibits the enhancement by cyclophosphamide of experimental lung metastasis of human fibrosarcoma cells.

Abstract

Tumor cells must attach themselves to basement membranes, through which they degrade and migrate, in order to spread to distant sites. If vascular endothelial cells are damaged by pretreatment with anticancer drugs and the subendothelial basement membranes are exposed, the attachment of malignant cells to basement membranes and subsequent metastasis formation in some tissues may be enhanced. In this study, the pretreatment of endothelial cell monolayers and mice with cyclophosphamide (CPA) was respectively shown to promote the adhesion of HT1080 human fibrosarcoma cells to endothelial cell monolayers in vitro and lung colonization in vivo. YIGSR, a synthetic laminin pentapeptide, inhibited the enhancement of lung colonization by CPA when it was co-injected intravenously with tumor cells. This inhibitory effect of YIGSR may be due to a reduction in the adhesion of HT1080 cells to injured blood vessel walls since YIGSR inhibited both the adhesion of HT1080 cells to CPA-treated endothelial cell monolayers and the invasion through basement membranes in vitro.