Background: Chemoresistance is an important issue to be solved in breast cancer. It is well known that the content and morphology of collagens in tumor tissues are drastically altered following chemotherapy, and discoidin domain receptor 2 (DDR2) is a unique type of receptor tyrosine kinase (RTK). This RTK is activated by collagens, playing important roles in human malignancies. However, the contribution to the chemoresistance of DDR2 in terms of the association with collagens remains largely unclear in breast cancer.Methods: We immunolocalized DDR2 and collagen type I in 224 breast cancer tissues and subsequently conducted in vitro studies to confirm the role of DDR2 in breast cancer chemoresistance using chemosensitive and chemoresistant cell lines.Results: DDR2 immunoreactivity was positively correlated with aggressive behaviors of breast cancer and was significantly associated with an increased risk of recurrence, especially in those who received chemotherapy. Moreover, in vitro experiments demonstrated that DDR2 promoted the proliferative activity of breast cancer cells, and cell viability after epirubicin treatment was significantly maintained by DDR2 in a collagen I-dependent manner.Conclusions: These data suggested that DDR2 could be a poor prognostic factor associated with cell proliferation and chemotherapy resistance in human breast cancer.
背景：化疗耐药性是乳腺癌治疗中亟待解决的重要问题。已知化疗后肿瘤组织中胶原蛋白的含量和形态会发生显著改变，而盘状结构域受体2（DDR2）作为一种独特的受体酪氨酸激酶（RTK），其活性受胶原蛋白调控，在人类恶性肿瘤中发挥重要作用。然而，在乳腺癌中，DDR2如何通过与胶原蛋白的相互作用影响化疗耐药性，目前尚不明确。 方法：本研究对224例乳腺癌组织进行DDR2与I型胶原蛋白的免疫组化定位分析，并采用化疗敏感与耐药细胞系开展体外实验，以验证DDR2在乳腺癌化疗耐药中的作用。 结果：DDR2免疫反应性与乳腺癌侵袭性行为呈正相关，且与复发风险升高显著相关，在接受化疗的患者中尤为明显。体外实验进一步表明，DDR2能促进乳腺癌细胞增殖活性，并以I型胶原蛋白依赖的方式显著维持表柔比星处理后的细胞存活率。 结论：本研究提示DDR2可能通过促进细胞增殖和介导化疗耐药，成为乳腺癌不良预后的潜在标志物。
肿瘤(癌症)患者之家