Mok Samuel C, Bonome Tomas, Vathipadiekal Vinod, Bell Aaron, Johnson Michael E, Wong Kwong-kwok, Park Dong-Choon, Hao Ke, Yip Daniel K P, Donninger Howard, Ozbun Laurent, Samimi Goli, Brady John, Randonovich Mike, Pise-Masison Cindy A, Barrett J Carl, Wong Wing H, Welch William R, Berkowitz Ross S, Birrer Michael J
Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Cancer Cell. 2009 Dec 8;16(6):521-32. doi: 10.1016/j.ccr.2009.10.018.
Advanced stage papillary serous tumors of the ovary are responsible for the majority of ovarian cancer deaths, yet the molecular determinants modulating patient survival are poorly characterized. Here, we identify and validate a prognostic gene expression signature correlating with survival in a series of microdissected serous ovarian tumors. Independent evaluation confirmed the association of a prognostic gene microfibril-associated glycoprotein 2 (MAGP2) with poor prognosis, whereas in vitro mechanistic analyses demonstrated its ability to prolong tumor cell survival and stimulate endothelial cell motility and survival via the alpha(V)beta(3) integrin receptor. Increased MAGP2 expression correlated with microvessel density suggesting a proangiogenic role in vivo. Thus, MAGP2 may serve as a survival-associated target.
晚期卵巢乳头状浆液性肿瘤是导致大多数卵巢癌死亡的原因,但调节患者生存的分子决定因素却鲜为人知。在此,我们在一系列显微切割的浆液性卵巢肿瘤中鉴定并验证了一种与生存相关的预后基因表达特征。独立评估证实,预后基因微原纤维相关糖蛋白2(MAGP2)与不良预后相关,而体外机制分析表明,它能够通过α(V)β(3)整合素受体延长肿瘤细胞存活时间,并刺激内皮细胞迁移和存活。MAGP2表达增加与微血管密度相关,提示其在体内具有促血管生成作用。因此,MAGP2可能是一个与生存相关的靶点。