2012年9月5日 訊 /生物谷BIOON/ --腫瘤的生長依賴于其癌癥細胞和周圍正常組織或者癌癥基座的相互作用，間質細胞可以刺激腫瘤細胞的生長,，然而,，目前是否腫瘤細胞可以影響其基座細胞并不清楚,。
刊登在9月一期的國際雜志Journal of Clinical Investigation上的一年研究報告中，來自安德森癌癥研究中心的研究者報道了,，卵巢癌細胞可以激活HOXA9基因來強迫基座細胞產生可供腫瘤生長發(fā)育的環(huán)境,。
研究者Honami Naora和其同事發(fā)現，在卵巢癌病人和小鼠模型中,，HOXA9基因的表達和病人治療結果失敗直接關聯,，卵巢癌細胞中HOXA9基因的表達可以促使細胞產生一種名為TGF-β的蛋白質，該蛋白質隨后會誘導周圍的非癌性細胞產生供腫瘤發(fā)育的環(huán)境,。通過在卵巢癌細胞中阻礙TGF-β的表達可以明顯降低腫瘤細胞的生長,。
這項研究發(fā)現為我們提供了思路，我們可以以TGF-β為靶點來開發(fā)出治療卵巢癌的新型藥物,。（生物谷Bioon.com）
編譯自：Ovarian Cancer Cells Hijack Surrounding Tissues to Enhance Tumor Growth
doi:10.1172/JCI62229
PMC:
PMID:
HOXA9 promotes ovarian cancer growth by stimulating cancer-associated fibroblasts
Ko SY, Barengo N, Ladanyi A, Lee JS, Marini F, Lengyel E, Naora H.
Epithelial ovarian cancers (EOCs) often exhibit morphologic features of embryonic Müllerian duct-derived tissue lineages and colonize peritoneal surfaces that overlie connective and adipose tissues. However, the mechanisms that enable EOC cells to readily adapt to the peritoneal environment are poorly understood. In this study, we show that expression of HOXA9, a Müllerian-patterning gene, is strongly associated with poor outcomes in patients with EOC and in mouse xenograft models of EOC. Whereas HOXA9 promoted EOC growth in vivo, HOXA9 did not stimulate autonomous tumor cell growth in vitro. On the other hand, expression of HOXA9 in EOC cells induced normal peritoneal fibroblasts to express markers of cancer-associated fibroblasts (CAFs) and to stimulate growth of EOC and endothelial cells. Similarly, expression of HOXA9 in EOC cells induced normal adipose- and bone marrow-derived mesenchymal stem cells (MSCs) to acquire features of CAFs. These effects of HOXA9 were due in substantial part to its transcriptional activation of the gene encoding TGF-β2 that acted in a paracrine manner on peritoneal fibroblasts and MSCs to induce CXCL12, IL-6, and VEGF-A expression. These results indicate that HOXA9 expression in EOC cells promotes a microenvironment that is permissive for tumor growth.
