Majo Sandra, Courtois Sarah, Souleyreau Wilfried, Bikfalvi Andreas, Auguste Patrick
Université de Bordeaux, Bordeaux, France.
INSERM, U1035, Bordeaux, France.
Front Oncol. 2020 Apr 28;10:625. doi: 10.3389/fonc.2020.00625. eCollection 2020.
Renal cell carcinoma (RCC) represents the main renal tumors and are highly metastatic. They are heterogeneous tumors and are subdivided in 12 different subtypes where clear cell RCC (ccRCC) represents the main subtype. Tumor extracellular matrix (ECM) is composed, in RCC, mainly of different fibrillar collagens, fibronectin, and components of the basement membrane such as laminin, collagen IV, and heparan sulfate proteoglycan. Little is known about the role of these ECM components on RCC cell behavior. Analysis from The Human Protein Atlas dataset shows that high collagen 1 or 4A2, fibronectin, entactin, or syndecan 3 expression is associated with poor prognosis whereas high collagen 4A3, syndecan 4, or glypican 4 expression is associated with increased patient survival. We then analyzed the impact of collagen 1, fibronectin 1 or Matrigel on three different RCC cell lines (Renca, 786-O and Caki-2) . We found that all the different matrices have little effect on RCC cell proliferation. The three cell lines adhere differently on the three matrices, suggesting the involvement of a different set of integrins. Among the 3 matrices tested, collagen 1 is the only component able to increase migration in the three cell lines as well as MMP-2 and 9 activity. Moreover, collagen 1 induces MMP-2 mRNA expression and is implicated in the epithelial to mesenchymal transition of two RCC cell lines via Zeb2 (Renca) or Snail 2 (Caki-2) mRNA expression. Taken together, our results show that collagen 1 is the main component of the ECM that enhances tumor cell invasion in RCC, which is important for the metastasic process.
肾细胞癌（RCC）是主要的肾脏肿瘤，具有高度转移性。它们是异质性肿瘤，可细分为12种不同亚型，其中透明细胞肾细胞癌（ccRCC）是主要亚型。在RCC中，肿瘤细胞外基质（ECM）主要由不同的纤维状胶原蛋白、纤连蛋白以及基底膜成分如层粘连蛋白、IV型胶原蛋白和硫酸乙酰肝素蛋白聚糖组成。关于这些ECM成分对RCC细胞行为的作用知之甚少。来自人类蛋白质图谱数据集的分析表明，高表达的胶原蛋白1或4A2、纤连蛋白、巢蛋白或多功能蛋白聚糖3与不良预后相关，而高表达的胶原蛋白4A3、多功能蛋白聚糖4或磷脂酰肌醇蛋白聚糖4与患者生存率增加相关。然后，我们分析了胶原蛋白1、纤连蛋白1或基质胶对三种不同的RCC细胞系（Renca、786 - O和Caki - 2）的影响。我们发现所有不同的基质对RCC细胞增殖影响很小。这三种细胞系在三种基质上的黏附方式不同，表明涉及不同的整合素组。在测试的3种基质中，胶原蛋白1是唯一能够增加这三种细胞系迁移以及MMP - 2和9活性的成分。此外，胶原蛋白1诱导MMP - 2 mRNA表达，并通过Zeb2（Renca）或Snail 2（Caki - 2）mRNA表达参与两种RCC细胞系的上皮 - 间质转化。综上所述，我们的结果表明胶原蛋白1是ECM中增强RCC肿瘤细胞侵袭的主要成分，这对转移过程很重要。
