2012年9月5日 訊 /生物谷BIOON/ --腫瘤的生長(zhǎng)依賴于其癌癥細(xì)胞和周圍正常組織或者癌癥基座的相互作用,，間質(zhì)細(xì)胞可以刺激腫瘤細(xì)胞的生長(zhǎng),，然而，目前是否腫瘤細(xì)胞可以影響其基座細(xì)胞并不清楚,。
刊登在9月一期的國(guó)際雜志Journal of Clinical Investigation上的一年研究報(bào)告中,，來自安德森癌癥研究中心的研究者報(bào)道了，卵巢癌細(xì)胞可以激活HOXA9基因來強(qiáng)迫基座細(xì)胞產(chǎn)生可供腫瘤生長(zhǎng)發(fā)育的環(huán)境,。
研究者Honami Naora和其同事發(fā)現(xiàn),，在卵巢癌病人和小鼠模型中，HOXA9基因的表達(dá)和病人治療結(jié)果失敗直接關(guān)聯(lián),，卵巢癌細(xì)胞中HOXA9基因的表達(dá)可以促使細(xì)胞產(chǎn)生一種名為TGF-β的蛋白質(zhì),，該蛋白質(zhì)隨后會(huì)誘導(dǎo)周圍的非癌性細(xì)胞產(chǎn)生供腫瘤發(fā)育的環(huán)境。通過在卵巢癌細(xì)胞中阻礙TGF-β的表達(dá)可以明顯降低腫瘤細(xì)胞的生長(zhǎng),。
這項(xiàng)研究發(fā)現(xiàn)為我們提供了思路,，我們可以以TGF-β為靶點(diǎn)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.
