PDF(Pubmed)
Abstract：
CD105 (endoglin) is a transmembrane protein that functions as a TGF-beta coreceptor and is highly expressed on endothelial cells. Unsurprisingly, preclinical and clinical evidence strongly suggests that CD105 is an important contributor to tumor angiogenesis and tumor progression. Emerging evidence suggests that CD105 is also expressed by tumor cells themselves in certain cancers such as renal cell carcinoma (RCC). In human RCC tumor cells, CD105 expression is associated with stem cell-like properties and contributes to the malignant phenotype in vitro and in xenograft models. However, as a regulator of TGF-beta signaling, there is a striking lack of evidence for the role of tumor-expressed CD105 in the anti-tumor immune response and the tumor microenvironment. In this study, we report that tumor cell-expressed CD105 potentiates both the in vitro and in vivo tumorigenic potential of RCC in a syngeneic murine RCC tumor model. Importantly, we find that tumor cell-expressed CD105 sculpts the tumor microenvironment by enhancing the recruitment of immunosuppressive cell types and inhibiting the polyfunctionality of tumor-infiltrating CD4+ and CD8+ T cells. Finally, while CD105 expression by endothelial cells is a well-established contributor to tumor angiogenesis, we also find that tumor cell-expressed CD105 significantly contributes to tumor angiogenesis in RCC.
摘要：
CD105(endoglin)是作为TGF-β共受体起作用的跨膜蛋白,并且在内皮细胞上高度表达。毫不奇怪,临床前和临床证据强烈表明，CD105是肿瘤血管生成和肿瘤进展的重要因素。新出现的证据表明,CD105在某些癌症例如肾细胞癌(RCC)中也由肿瘤细胞本身表达。在人RCC肿瘤细胞中，CD105表达与干细胞样特性相关，并有助于体外和异种移植模型中的恶性表型。然而,作为TGF-β信号的调节剂，对于肿瘤表达的CD105在抗肿瘤免疫应答和肿瘤微环境中的作用,目前尚缺乏证据.在这项研究中,我们报道，肿瘤细胞表达的CD105在同基因鼠RCC肿瘤模型中增强了RCC的体外和体内致瘤潜力。重要的是,我们发现，肿瘤细胞表达的CD105通过增强免疫抑制细胞类型的募集和抑制肿瘤浸润的CD4+和CD8+T细胞的多功能性来塑造肿瘤微环境。最后,虽然内皮细胞的CD105表达是肿瘤血管生成的公认因素，我们还发现肿瘤细胞表达的CD105在RCC中显著促进肿瘤血管生成。
