科学家揭示卵巢癌细胞“劫持”周边细胞的分子机理
肿瘤的生长依赖于其癌症细胞和周围正常组织或者癌症基座的相互作用，间质细胞可以刺激肿瘤细胞的生长，然而，目前是否肿瘤细胞可以影响其周边细胞并不清楚。
安德森癌症研究中心的研究者报道，卵巢癌细胞可以激活HOXA9基因来强迫周边细胞产生可供肿瘤生长发育的环境，相关研究刊登在9月的国际杂志Journal of Clinical Investigation上。
Honami Naora发现，在卵巢癌病人和小鼠模型中，HOXA9基因的表达和病人治疗结果失败直接关联，卵巢癌细胞中HOXA9基因的表达可以促使细胞产生一种名为TGF-β的蛋白质，该蛋白质随后会诱导周围的非癌性细胞产生供肿瘤发育的环境。通过在卵巢癌细胞中阻碍TGF-β的表达可以明显降低肿瘤细胞的生长。
这项研究发现为我们提供了思路，我们可以以TGF-β为靶点来开发出治疗卵巢癌的新型药物。
>>延伸阅读：另一种“挟持”的分子机制
RNA病毒劫持宿主细胞进行增殖机制
Bert Semler教授领导的新研究中，加州大学欧文分校研究人员和丹麦同事们发现某些RNA病毒劫持人细胞中的一种关键性DNA修复酶从而产生用于它们进行复制时所必需的遗传物质。
多年来，科学家们已经知道病毒利用它们的宿主细胞提供的功能来增加它们的数目，但是这项研究是第一次鉴定出含有RNA的小核糖核酸病毒(picornavirus)利用一种DNA修复酶来进行复制。
通过靶向病毒复制而不是病毒本身所需的宿主细胞功能，人们可能就能够避免病毒对抗病毒药物产生耐药性。
为了存活，RNA病毒经常发生突变，因此旨在对抗它们的药物通常随着时间的流逝而变得没有疗效。比如，HIV快速发生突变，从而使得利用多种抗病毒药物的组合疗法成为必需。
HOXA9 promotes ovarian cancer growth by stimulating cancer-associated fibroblasts
Song Yi Ko, Nicolas Barengo, Andras Ladanyi, Ju-Seog Lee, Frank Marini, Ernst Lengyel and Honami Naora
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.
文献链接：HOXA9 promotes ovarian cancer growth by stimulating cancer-associated fibroblasts
