科學(xué)家早已證實(shí)無(wú)機(jī)砷是一種人類(lèi)致癌劑。另外,，越來(lái)越多的證據(jù)提示著癌癥是一種基于干細(xì)胞的疾病,。正常的干細(xì)胞是組織再生和有機(jī)體維持穩(wěn)定性所必需的。但是癌干細(xì)胞被認(rèn)為是腫瘤形成,、生長(zhǎng)和擴(kuò)散的驅(qū)動(dòng)力,。
來(lái)自美國(guó)國(guó)家環(huán)境衛(wèi)生科學(xué)研究所分支機(jī)構(gòu)國(guó)家環(huán)境衛(wèi)生科學(xué)研究所(National Institute of Environmental Health Sciences)國(guó)家毒理檢測(cè)實(shí)驗(yàn)室(National Toxicology Program Laboratory)的Michael Waalkes博士和他的研究小組之前已經(jīng)發(fā)現(xiàn)正常細(xì)胞當(dāng)用無(wú)機(jī)砷處理后就變成癌細(xì)胞。在這項(xiàng)新研究中,，研究人員發(fā)現(xiàn)當(dāng)把這些癌細(xì)胞放在正常的干細(xì)胞附近而且不相互接觸時(shí),，這些正常的干細(xì)胞非常快地獲得癌干細(xì)胞的特征,。這就證實(shí)癌細(xì)胞能夠通過(guò)半通透性細(xì)胞膜發(fā)送分子信號(hào),，從而將正常的干細(xì)胞變成癌干細(xì)胞,。
這篇論文證實(shí)癌癥能夠通過(guò)招募附近的正常干細(xì)胞并過(guò)量產(chǎn)生癌干細(xì)胞來(lái)進(jìn)行增殖,。招募正常的干細(xì)胞并將之變成癌干細(xì)胞可能在包括癌癥生長(zhǎng)和轉(zhuǎn)移在內(nèi)的致癌過(guò)程中產(chǎn)生極其廣泛的影響。這也意味著干細(xì)胞有助于解釋致癌作用的產(chǎn)生機(jī)理,，而且它們也可能是其他慢性疾病的影響因素,。
這些發(fā)現(xiàn)揭示砷致癌的一個(gè)潛在重要性的機(jī)制，可能有助于解釋一些研究砷的研究人員的觀察結(jié)果：砷經(jīng)常導(dǎo)致多種類(lèi)型的腫瘤在皮膚上或身體內(nèi)形成,。
在這項(xiàng)研究中,，研究人員使用前列腺干細(xì)胞系而不是胚胎干細(xì)胞來(lái)進(jìn)行研究。相關(guān)研究結(jié)果于2012年4月4日在線發(fā)表在Environmental Health Perspectives期刊上,。(生物谷：towersimper編譯)
doi:10.1289/ehp.1204987
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Arsenic-Transformed Malignant Prostate Epithelia Can Convert Noncontiguous Normal Stem Cells into an Oncogenic Phenotype
Yuanyuan Xu, Erik J. Tokar, Yang Sun, Michael P. Waalkes
Background: Cancer stem cells (CSCs) are likely critical to carcinogenesis, and, like normal stem cells (NSCs), are impacted by microenvironment. Malignant cells release extracellular factors modifying tumor behavior. Inorganic arsenic, a human carcinogen, over-produces CSCs in various model systems of carcinogenesis. Here, we determine if NSCs are influenced by nearby arsenic-transformed malignant epithelial cells (MECs) as a possible factor in arsenic associated CSC overabundance.
Methods: Transwell non-contact co-culture allowed the study of the effects of non-contiguous, arsenic-transformed prostate MECs on the isogenic human prostate NSC line, WPE-stem. Cancer phenotype was assessed by secreted MMPs, invasiveness, colony formation and spheroid formation. Gene expression was assessed at the protein (western blot) or mRNA (RT-PCR) levels.
Results: Non-contact co-culture of MECs and NSCs rapidly (≤ 3 weeks) caused hyper-secretion of MMPs and marked suppression of the tumor suppressor gene PTEN in NSCs. NSCs co-cultured with MECs also showed increased invasiveness and clonogenicity and formed more free-floating spheroids and highly branched ductal-like structures in Matrigel, all typical for CSCs. MEC co-culture caused dysregulated self-renewal and differentiation-related gene expression patterns and epithelial-to-mesenchymal transition in NSCs consistent with acquired cancer phenotype. Interleukin-6, a cytokine involved in tumor microenvironment control, was hyper-secreted by MECs and interleukin-6 exposure duplicated several responses in NSCs of conversion to CSCs via MEC co-culture (MMP hyper-secretion, decreased PTEN, etc.).
Conclusions: These results indicate that arsenic-transformed MECs recruit nearby NSCs into a cancer phenotype thereby potentially increasing CSC number. This may be a factor in arsenic-induced CSC overabundance seen in multiple model systems.
