Popielarski Marcin, Ponamarczuk Halszka, Stasiak Marta, Watała Cezary, Świątkowska Maria
Department of Cytobiology and Proteomics, Medical University of Lodz 6/8 Mazowiecka St., 92-215 Lodz, Poland.
Department of Haemostatic Disorders, Medical University of Lodz 6/8 Mazowiecka St., 92-215 Lodz, Poland.
Am J Cancer Res. 2019 Aug 1;9(8):1554-1582. eCollection 2019.
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 and αβ 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.
癌症转移涉及癌细胞与内皮细胞的黏附。这一过程可由整合素介导，整合素是负责与细胞外基质（ECM）蛋白相互作用的表面受体。整合素β和αβ是参与癌症进展和转移的因素。蛋白二硫键异构酶（PDI）引发的硫醇-二硫键交换可促进整合素的激活。本研究的目的是证明在癌细胞通过内皮细胞黏附和迁移过程中，二硫键重排在整合素分子中的作用。我们提供的证据表明，高转移性的MDA-MB-231乳腺癌细胞系比非侵袭性的MCF-10A和MCF-7细胞系更有效地黏附于内皮细胞，并且MDA-MB-231与内皮细胞的黏附可被阻断游离巯基的试剂（二硫苏糖醇、胱胺或对氯汞苯甲酸）或PDI抑制剂（Q3Rut、16F16或PACMA-31）减弱。此外，我们证明MDA-MB-231细胞的跨内皮迁移和胶原蛋白的收缩可被硫醇阻断剂或PDI抑制剂阻断，并且这些因素会影响整合素分子上游离巯基的暴露。
