Liu Yajun, Sowa Grzegorz
Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65212.
Cancer Cell Microenviron. 2014;1(6). doi: 10.14800/ccm.439.
In addition to cancer cells, primary tumors are composed of a multitude of stromal cell types. Among others, the stromal cell types involved in tumor growth and progression include endothelial cells, fibroblasts, pericytes, stem cells and various cell types of immune origin. While the role of oncogenes or tumor suppressor proteins expressed in cancer cells has been extensively studied, far less is known about potential involvement of proteins expressed in stromal cell types present within the tumor microenvironment. Recent experimental evidence from our laboratory suggests that caveolin-2 (Cav-2) protein expressed in stromal cell types of the tumor microenvironment promotes subcutaneous tumor growth in two independent syngeneic mouse models, i.e., Lewis lung carcinoma (LLC) and B16-F10 melanoma. Mechanistically, the tumor growth promoting role of Cav-2 is associated with enhanced tumor induced neovascularization. At the molecular level, host-expressed Cav-2 appears to prevent excessive expression of anti-angiogenic thrombospondin-1 (TSP-1) and promote phosphorylation of pro-angiogenic endothelial nitric oxide synthase (eNOS) at serine 1177. Taken together, our recent findings suggest that Cav-2 expressed within the tumor microenvironment could be a potential target for anti-cancer therapy.
除癌细胞外，原发性肿瘤还由多种基质细胞类型组成。其中，参与肿瘤生长和进展的基质细胞类型包括内皮细胞、成纤维细胞、周细胞、干细胞以及各种免疫来源的细胞类型。虽然癌细胞中表达的癌基因或肿瘤抑制蛋白的作用已得到广泛研究，但对于肿瘤微环境中存在的基质细胞类型所表达的蛋白质的潜在作用却知之甚少。我们实验室最近的实验证据表明，肿瘤微环境的基质细胞类型中表达的小窝蛋白-2（Cav-2）蛋白在两种独立的同基因小鼠模型，即Lewis肺癌（LLC）和B16-F10黑色素瘤中促进皮下肿瘤生长。从机制上讲，Cav-2促进肿瘤生长的作用与增强肿瘤诱导的新血管形成有关。在分子水平上，宿主表达的Cav-2似乎可防止抗血管生成的血小板反应蛋白-1（TSP-1）过度表达，并促进促血管生成的内皮型一氧化氮合酶（eNOS）在丝氨酸1177处的磷酸化。综上所述，我们最近的研究结果表明，肿瘤微环境中表达的Cav-2可能是抗癌治疗的潜在靶点。
