耶魯大學(xué)醫(yī)學(xué)院的研究人員發(fā)現(xiàn)了一種卵巢癌干細(xì)胞因子，與卵巢癌的生長(zhǎng)和病人的預(yù)后之間存在關(guān)鍵聯(lián)系。新研究為開發(fā)新的靶向卵巢癌治療方法鋪平了道路，相關(guān)研究成果發(fā)表在最新一期的Cell Cycle雜志上。

    研究領(lǐng)導(dǎo)者產(chǎn)科，婦科及生殖科學(xué)系的副教授Yingqun Huang和她的同事已經(jīng)證明這兩個(gè)概念之間的聯(lián)系，徹底改變了卵巢癌的治療。

    首先是“癌干細(xì)胞”的概念，癌干細(xì)胞是難以識(shí)別的一個(gè)小的腫瘤細(xì)胞子集，能促進(jìn)大部分腫瘤的生長(zhǎng)。普通的治療方法通常會(huì)殺死大部分腫瘤細(xì)胞，而干細(xì)胞會(huì)持續(xù)增長(zhǎng)。第二個(gè)概念被稱為“種子和土壤”，即腫瘤細(xì)胞的“微環(huán)境”，這是癌細(xì)胞的生長(zhǎng)和擴(kuò)散需要的特殊環(huán)境。這兩個(gè)概念都用于治療成人實(shí)體腫瘤如卵巢癌，卵巢癌一直是出了名的難以診斷和治療。卵巢癌患者往往因?qū)熌退幍哪[瘤細(xì)胞復(fù)發(fā)，最終導(dǎo)致癌細(xì)胞生長(zhǎng)失控，患者死亡。

    在這項(xiàng)研究中，研究人員能夠確定卵巢癌中這兩個(gè)概念之間相互影響的分子基礎(chǔ)。他們通過(guò)使用先進(jìn)的基因測(cè)序方法，證明干細(xì)胞因子Lin28和骨形態(tài)發(fā)生蛋白4（BMP4）信號(hào)分子之間的相互調(diào)控聯(lián)系。

    這些結(jié)果被最新一些分子卵巢癌的預(yù)后數(shù)據(jù)證實(shí)，這也表明腫瘤微環(huán)境在卵巢癌變中發(fā)揮積極的作用。總之，新研究發(fā)現(xiàn)新了癌癥治療的新靶點(diǎn)。

    Lin28 regulates BMP4 and functions with Oct4 to affect ovarian tumor microenvironment

    Wei Ma, Jing Ma, Jie Xu, Chong Qiao, Adam Branscum, Andres Cardenas, Andre T. Baron, Peter Schwartz, Nita J. Maihle and Yingqun Huang

   Emerging evidence suggests that the tumor microenvironment plays a critical role in regulating cancer stem cells (CSCs) and tumor progression through both autocrine and paracrine signaling. Elevated production of bone morphogenetic proteins (BMPs) from human ovarian cancer cells and stroma has been shown to increase CSC proliferation and tumor growth. Here, we report that Lin28, a stem cell factor, binds to BMP4 mRNA in epithelial ovarian carcinoma cells, thereby promoting BMP4 expression at the post-transc**tional level. As co-expression of Lin28 and Oct4 (another stem cell factor) has been implicated in ovarian cancer CSCs, we also determined that high levels of Lin28 are associated with an unfavorable prognosis when co-expressed with high levels of Oct4. Together, these findings uncover a new level of regulation of BMP4 expression and imply a novel Lin28/Oct4/BMP4-mediated mechanism of regulating ovarian tumor cell growth, thus holding potential for the development of new strategies for the diagnosis and treatment of ovarian cancer.