Pérez-Díaz Sergio, Lindberg Jessica, Anerillas Luis Oliveros, Kingham Paul J, Sund Malin, Rask Gunilla, Svensson Johan, Jansson Malin, Wiberg Rebecca
Department of Medical and Translational Biology, Umeå University, Umeå, SE-901 87, Sweden.
Department of Laboratory Medicine, Division of Clinical Physiology, Karolinska Institute, Stockholm, Sweden.
Cancer Cell Int. 2024 Jul 20;24(1):254. doi: 10.1186/s12935-024-03449-4.
Breast cancer is the most common cancer in women. Cancer cells can persist in a prolonged dormant state for years without any clinical evidence of disease creating an urgent need to better understand the molecular mechanisms leading to relapse. This study aimed to identify extracellular matrix (ECM) components associated with hypoxia-induced breast cancer dormancy. The effects of selected ECM proteins on breast cancer cell proliferation were analyzed, along with their correlation with established prognostic markers in human breast cancer tissue.
Screening of extracellular matrix proteins was performed in hypoxia-induced dormant MCF-7 breast cancer cells. Proliferation of MCF-7 cells in vitro was subsequently determined in the presence of recombinant ColVII. Adipose tissue-derived mesenchymal stem cells (AdMSCs) subpopulation overexpressing ColVII were indirectly isolated by ColVII receptor integrin-α6 specific antibodies. AdMSCs- MCF-7 3D spheroid cultures were generated to model solid tumour conditions. In addition, the association between ColVII and various prognostic markers was evaluated in clinical samples of human breast cancer tissue.
Dormant MCF-7 cells showed an elevated expression of ColVII while MCF-7 cells cultured on ColVII exhibited reduced proliferation in vitro. In AdMSCs-MCF-7 3D spheroids, a reduced proliferation of MCF-7 cells was observed in Int-α6/ ColVII compared with Int-α6 ColVII AdMSCs spheroids. In human tissue, high ColVII expression correlated to several positive prognostic markers. Staining for Cytokeratin-5 revealed that ColVII-expressing cells were predominantly myoepithelial cells.
ColVII is associated with reduced proliferation of breast cancer cells in vitro. ColVII is strongly expressed in myoepithelial cells and in breast cancer tissue the high ColVII expression correlates with several well-known positive prognostic markers, highlighting its potential as a prognostic marker in breast cancer.
乳腺癌是女性中最常见的癌症。癌细胞可长期处于休眠状态数年，而无任何疾病的临床证据，这迫切需要更好地了解导致复发的分子机制。本研究旨在鉴定与缺氧诱导的乳腺癌休眠相关的细胞外基质（ECM）成分。分析了所选ECM蛋白对乳腺癌细胞增殖的影响，以及它们与人类乳腺癌组织中已确立的预后标志物的相关性。
在缺氧诱导的休眠MCF-7乳腺癌细胞中进行细胞外基质蛋白筛选。随后在重组VII型胶原存在的情况下测定MCF-7细胞在体外的增殖情况。通过VII型胶原受体整合素-α6特异性抗体间接分离过表达VII型胶原的脂肪组织来源间充质干细胞（AdMSCs）亚群。生成AdMSCs-MCF-7三维球体培养物以模拟实体瘤情况。此外，在人类乳腺癌组织的临床样本中评估VII型胶原与各种预后标志物之间的关联。
休眠的MCF-7细胞显示VII型胶原表达升高，而在VII型胶原上培养的MCF-7细胞在体外增殖减少。在AdMSCs-MCF-7三维球体中，与整合素-α6/VII型胶原AdMSCs球体相比，在整合素-α6/ VII型胶原中观察到MCF-7细胞增殖减少。在人体组织中，高VII型胶原表达与几种阳性预后标志物相关。细胞角蛋白-5染色显示，表达VII型胶原的细胞主要是肌上皮细胞。
VII型胶原与体外乳腺癌细胞增殖减少有关。VII型胶原在肌上皮细胞中强烈表达，在乳腺癌组织中，高VII型胶原表达与几种众所周知的阳性预后标志物相关，突出了其作为乳腺癌预后标志物的潜力。
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