Modifications of disulfide bonds in breast cancer cell migration and invasiveness

摘要

Cancer metastasis involves the adhesion of cancer cells to the endothelium. This process can be mediated by integrins which are surface receptors responsible for interactions with ECM proteins. Integrins β 1 and α V β 3 represent factors are involved in cancer progression and metastasis. Activation of integrins can be promoted by thiol-disulfide exchanges initiated by Protein Disulfide Isomerase (PDI). The purpose of this study was to prove the involvement of disulfide rearrangements in the molecules of integrins in the course of cancer cell adhesion and migration through the endothelium. We present the evidence which proves that highly metastatic MDA-MB-231 breast cancer cell lines adhere to endothelial cells are more effective than non-invasive MCF-10A and MCF-7 cell lines and that the attachment of MDA-MB-231 to the endothelium can be attenuated either by the agents blocking free thiol groups (DTNB, cystamine or PCMBS) or by PDI inhibitors (Q3Rut, 16F16 or PACMA-31). Furthermore, we prove that the transendothelial migration of MDA-MB-231 cells and contraction of collagen can be blocked by thiol blockers or PDI inhibitors and that these factors affect exposition of free thiols on integrin molecules.