在脂肪干細(xì)胞不存在(左)和存在(右)時(shí),，腫瘤大小和膠原纖維排列，圖片來(lái)自Claudia Fischbach-Teschl實(shí)驗(yàn)室,。
在進(jìn)行乳房切除和其他腫瘤切除治療之后,，經(jīng)常被用于重建手術(shù)的干細(xì)胞可能也會(huì)造成危險(xiǎn)：美國(guó)康奈爾大學(xué)生物醫(yī)學(xué)研究人員發(fā)現(xiàn)這些干細(xì)胞與即便是微量的癌細(xì)胞接觸，也能夠會(huì)產(chǎn)生一種適合更多腫瘤生長(zhǎng)的微環(huán)境,。
在這項(xiàng)于6月4日在線發(fā)表在PNAS期刊上的最新研究中,，研究人員所使用的干細(xì)胞來(lái)源于脂肪，因而被稱為脂肪干細(xì)胞(adipose-derived stem cell).它們非常適合用于組織再生和重建手術(shù),，這是因?yàn)樗鼈兎浅：玫爻袚?dān)起健康組織的功能和招募新的血管來(lái)促進(jìn)愈合,。
但是，康奈爾大學(xué)研究人員觀察到癌細(xì)胞基質(zhì)---含有腫瘤細(xì)胞分泌的化學(xué)物的可溶性物質(zhì)---的存在能夠阻止脂肪干細(xì)胞按照期望中的那樣變成脂肪細(xì)胞,。相反,，這種癌細(xì)胞基質(zhì)觸發(fā)這些干細(xì)胞分泌出促進(jìn)血管形成的化學(xué)因子，并觸發(fā)它們發(fā)展為肌成纖維細(xì)胞(myofibroblast),，而已知肌成纖維細(xì)胞在腫瘤發(fā)展中發(fā)揮著作用,。
這些變化導(dǎo)致包圍著脂肪干細(xì)胞的胞外基質(zhì)硬化---硬化是乳腺癌的一個(gè)典型特征。肌成纖維細(xì)胞使得使得周圍的組織變得堅(jiān)硬起來(lái),，這種堅(jiān)硬觸發(fā)脂肪干細(xì)胞行為發(fā)生更多的變化,，而這種變化又導(dǎo)致它們產(chǎn)生更加多的促進(jìn)腫瘤發(fā)展的特征。
在體外利用干細(xì)胞和侵襲性程度不同的乳腺癌細(xì)胞系開(kāi)展的實(shí)驗(yàn)中,，研究人員觀察到這些變化,。他們首先收集來(lái)自腫瘤細(xì)胞的可溶性基質(zhì)，并觀察脂肪干細(xì)胞對(duì)這種基質(zhì)作出的反應(yīng)后如何發(fā)生改變,。他們發(fā)現(xiàn)TGF-β和IL-8是特異性的腫瘤分泌因子,，促進(jìn)這些干細(xì)胞在表型上最終變化為肌成纖維細(xì)胞。他們通過(guò)注射干細(xì)胞和腫瘤細(xì)胞到小鼠乳腺中而在體內(nèi)證實(shí)這些實(shí)驗(yàn)結(jié)果,。
事實(shí)上,，肥胖的婦女更可能患上乳腺癌，這也支持這項(xiàng)研究中的實(shí)驗(yàn)結(jié)果,。更多脂肪組織的存在意味著更多的脂肪干細(xì)胞,，因此人們可以推測(cè)更大的干細(xì)胞池可能促進(jìn)腫瘤發(fā)展過(guò)程。(生物谷：ZinFingerNase編譯)
doi:10.1073/pnas.1121160109
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Implanted adipose progenitor cells as physicochemical regulators of breast cancer
Emily M. Chandlera,1, Bo Ri Seoa,1, Joseph P. Califanoa, Roberto C. Andresen Eguiluzb, Jason S. Leea, Christine J. Yoona, David T. Timsa, James X. Wanga, Le Chengc, Sunish Mohananc, Mark R. Buckleyd, Itai Cohend, Alexander Yu Nikitinc, Rebecca M. Williamsa, Delphine Gourdonb, Cynthia A. Reinhart-Kinga, and Claudia Fischbach
Multipotent adipose-derived stem cells (ASCs) are increasingly used for regenerative purposes such as soft tissue reconstruction following mastectomy; however, the ability of tumors to commandeer ASC functions to advance tumor progression is not well understood. Through the integration of physical sciences and oncology approaches we investigated the capability of tumor-derived chemical and mechanical cues to enhance ASC-mediated contributions to tumor stroma formation. Our results indicate that soluble factors from breast cancer cells inhibit adipogenic differentiation while increasing proliferation, proangiogenic factor secretion, and myofibroblastic differentiation of ASCs. This altered ASC phenotype led to varied extracellular matrix (ECM) deposition and contraction thereby enhancing tissue stiffness, a characteristic feature of breast tumors. Increased stiffness, in turn, facilitated changes in ASC behavior similar to those observed with tumor-derived chemical cues. Orthotopic mouse studies further confirmed the pathological relevance of ASCs in tumor progression and stiffness in vivo. In summary, altered ASC behavior can promote tumorigenesis and, thus, their implementation for regenerative therapy should be carefully considered in patients previously treated for cancer.
