在撒哈拉南部非洲,宮頸癌是一種主要引起婦女死因的癌癥。廣泛的證據(jù)表明,,宮頸癌及其癌前病變是由人乳頭瘤病毒(HPV)的感染引起,。雖然絕大多數(shù)的HPV的感染是自然感染的,根除感染細(xì)胞的失敗被表明會(huì)促進(jìn)病毒存留以及腫瘤發(fā)生,。
緊跟著致瘤性轉(zhuǎn)化,通過直接或者是體循環(huán)的方式暴露在炎癥因子中時(shí),,可能會(huì)增強(qiáng)宮頸上皮細(xì)胞疾病的發(fā)展,。總所周知,,精漿(SP) 包含了大量的炎癥介質(zhì),,它們都被鑒定為腫瘤生長有關(guān)的調(diào)節(jié)因子。近日,,來自南非開普頓大學(xué)的Arieh A. Katz等人研究了開展了一項(xiàng)有意義的研究,,即研究精漿在調(diào)節(jié)宮頸上皮細(xì)胞生長和腫瘤發(fā)生中的作用。研究發(fā)現(xiàn),,精漿可以明顯增強(qiáng)子宮頸癌細(xì)胞增殖以及腫瘤生長,。相關(guān)研究發(fā)表在3月19號美國《公共科學(xué)圖書館·綜合》(PLoS One)上。
本次研究Arieh A. Katz利用了海拉細(xì)宮頸癌細(xì)胞,,結(jié)果發(fā)現(xiàn)精漿(SP)引起了細(xì)胞內(nèi)炎性酶,,前列腺素內(nèi)過氧化物合酶(PTGS1和PTGS2),IL-1及IL-11,,血管內(nèi)皮生長因子A(VEGF-A)的表達(dá),。為了研究在活體內(nèi)精漿對腫瘤細(xì)胞生長的作用,他們異種移植海拉細(xì)胞于裸鼠的背部側(cè)面皮下,。研究發(fā)現(xiàn),,SP可以快速而明顯的提高腫瘤生長率以及增大海拉細(xì)胞在裸鼠中的大小。檢測發(fā)現(xiàn),,SP引起了體內(nèi)的PTGS酶,,細(xì)胞因子以及VEGF-A的表達(dá)。進(jìn)一步研究發(fā)現(xiàn),,SP增大了這些裸鼠的血管,。
結(jié)果表明,精漿確實(shí)增強(qiáng)子宮頸癌細(xì)胞增殖以及腫瘤生長,。另外,,SP引起的細(xì)胞因子的產(chǎn)生,VEGF-A的表達(dá)以及細(xì)胞增殖被PTGS通路所調(diào)節(jié),。(生物谷Deepblue編譯)
doi: 10.1371/journal.pone.0033848
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Seminal Plasma Enhances Cervical Adenocarcinoma Cell Proliferation and Tumour Growth In Vivo
Jason R. Sutherland, Kurt J. Sales, Henry N. Jabbour, Arieh A. Katzl.
Cervical cancer is one of the leading causes of cancer-related death in women in sub-Saharan Africa. Extensive evidence has shown that cervical cancer and its precursor lesions are caused by Human papillomavirus (HPV) infection. Although the vast majority of HPV infections are naturally resolved, failure to eradicate infected cells has been shown to promote viral persistence and tumorigenesis.Furthermore, following neoplastic transformation, exposure of cervical epithelial cells to inflammatory mediators either directly or via the systemic circulation may enhance progression of the disease. It is well recognised that seminal plasma contains an abundance of inflammatory mediators, which are identified as regulators of tumour growth. Here we investigated the role of seminal plasma in regulating neoplastic cervical epithelial cell growth and tumorigenesis.Using HeLa cervical adenocarcinoma cells, we found that seminal plasma (SP) induced the expression of the inflammatory enzymes, prostaglandin endoperoxide synthase (PTGS1 and PTGS2), cytokines interleukin (IL) -6, and -11 and vascular endothelial growth factor-A(VEGF-A). To investigate the role of SP on tumour cell growth in vivo, we xenografted HeLa cells subcutaneously into the dorsal flank of nude mice.Intra-peritoneal administration of SP rapidly and significantly enhanced the tumour growth rate and size of HeLa cell xenografts in nude mice. As observed in vitro, we found that SP induced expression of inflammatory PTGS enzymes, cytokines and VEGF-A in vivo. Furthermore we found that SP enhances blood vessel size in HeLa cell xenografts. Finally we show that SP-induced cytokine production, VEGF-A expression and cell proliferation are mediated via the induction of the inflammatory PTGS pathway.