Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cancer Manag Res. 2010 May 10;2:111-22. doi: 10.2147/cmar.s9835.
While prostate cancer is a common disease in men, it is uncommonly life-threatening. To better understand this phenomenon, tumor biologists have sought to elucidate the mechanisms that contribute to the development of virulent prostate cancer. The recent discovery that caveolin-1 (Cav-1) functions as an important oncogene involved in prostate cancer progression reflects the success of this effort. Cav-1 is a major structural coat protein of caveolae, specialized plasma membrane invaginations involved in multiple cellular functions, including molecular transport, cell adhesion, and signal transduction. Cav-1 is aberrantly overexpressed in human prostate cancer, with higher levels evident in metastatic versus primary sites. Intracellular Cav-1 promotes cell survival through activation of Akt and enhancement of additional growth factor pro-survival pathways. Cav-1 is also secreted as a biologically active molecule that promotes cell survival and angiogenesis within the tumor microenvironment. Secreted Cav-1 can be reproducibly detected in peripheral blood using a sensitive and specific immunoassay. Cav-1 levels distinguish men with prostate cancer from normal controls, and preoperative Cav-1 levels predict which patients are at highest risk for relapse following radical prostatectomy for localized disease. Thus, secreted Cav-1 is a promising biomarker in identifying clinically significant prostate cancer.
虽然前列腺癌是男性中常见的疾病,但它并不常见于危及生命的情况。为了更好地理解这一现象,肿瘤生物学家一直在努力阐明导致恶性前列腺癌发展的机制。最近发现,窖蛋白-1(Cav-1)作为一种参与前列腺癌进展的重要致癌基因,其功能得到了证实。Cav-1 是质膜凹陷小窝(caveolae)的主要结构外壳蛋白,凹陷小窝是参与多种细胞功能的特化质膜内陷,包括分子运输、细胞黏附和信号转导。Cav-1 在人类前列腺癌中过度表达,在转移性肿瘤中比原发性肿瘤中的表达水平更高。细胞内 Cav-1 通过激活 Akt 和增强其他生长因子促生存途径促进细胞存活。Cav-1 也作为一种具有生物活性的分子被分泌出来,在肿瘤微环境中促进细胞存活和血管生成。使用敏感和特异性免疫测定法可以在周围血液中重复检测到分泌型 Cav-1。Cav-1 水平可将患有前列腺癌的男性与正常对照组区分开来,术前 Cav-1 水平可预测哪些患者在接受根治性前列腺切除术治疗局限性疾病后复发的风险最高。因此,分泌型 Cav-1 是识别具有临床意义的前列腺癌的有前途的生物标志物。