近日,，來自新加坡的ASTAR醫(yī)學(xué)研究所,、新加坡基因組研究所和波士頓婦女醫(yī)院的研究人員發(fā)現(xiàn)了女性宮頸中一種特定類型的細胞是和HPV（人類乳頭瘤狀病毒）相關(guān)宮頸癌的主要促發(fā)因素,。而且這些特定細胞被切斷之后并不能夠再生,。相關(guān)研究成果刊登在國際著名雜志PNAS上,。
宮頸癌是新加坡常見的婦女第七大癌癥,，每年新增200例患者,。感染HPV是患宮頸癌的主要風(fēng)險因子,，HPV感染可以促使侵襲前癌癥，命名為CIN（宮頸上皮內(nèi)瘤樣病變）,，對于機體具有前癌性損害,，可以不斷發(fā)展，如果不及時治療容易引發(fā)擴散性癌癥,。
研究者Crum表示,，近10幾年來我們都不太清楚由HPV所引發(fā)的宮頸癌病例不斷上升，而且這種疾病僅僅是從宮頸不連續(xù)的區(qū)域（鱗狀柱狀上皮接合處）擴散的,。研究者的研究發(fā)現(xiàn)解開了這個謎底,，對于改造動物模型也帶來了巨大幫助。研究小組所發(fā)現(xiàn)的這種離散型的細胞位于宮頸口的鱗狀柱狀上皮接合處,，可以獨特表達其生物標(biāo)記物,，這就意味著這種細胞可以提供潛在的危險的損傷。
IMB的研究者Xian表示,，我們的研究也揭示了這種毒性細胞被切除后并不能夠再生,，這將幫助我們解釋經(jīng)過切除治療后HPV感染者低的發(fā)病率,。而且這項工作也驗證了研究者之前的工作，之前研究者揭示了某些癌癥源于一小類別的特殊細胞,。研究者Lane說：“總之,，這項研究為以后治療宮頸癌的療法提供了新的思路和更為深入的理解。（生物谷Bioon.com）
編譯自：Groundbreaking Discovery of the Cellular Origin of Cervical Cancer
編譯者：T.Shen
doi:10.1073/pnas.1202684109
PMC:
PMID:
A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer
Michael Herfsa,b, Yusuke Yamamotoc, Anna Lauryd, Xia Wange, Marisa R. Nuccia, Margaret E. McLaughlin-Drubinf, Karl Müngerf, Sarah Feldmang, Frank D. McKeonc,e,1, Wa Xiana,h,1,2, and Christopher P. Cruma,1,2
Infection by carcinogenic human papillomaviruses (HPV) results in precancers [cervical intraepithelial neoplasia (CIN)] and cancers near the ectoendocervical squamocolumnar (SC) junction of the cervix. However, the specific cells targeted by HPV have not been identified and the cellular origin of cervical cancer remains elusive. In this study, we uncovered a discrete population of SC junctional cells with unique morphology and gene-expression profile. We also demonstrated that the selected junctional biomarkers were expressed by a high percentage of high-grade CIN and cervical cancers associated with carcinogenic HPVs but rarely in ectocervical/transformation zone CINs or those associated with noncarcinogenic HPVs. That the original SC junction immunophenotype was not regenerated at new SC junctions following excision, not induced by expression of viral oncoproteins in foreskin keratinocytes, and not seen in HPV-related precursors of the vagina, vulva, and penis further support the notion that junctional cells are the source of cervical cancer. Taken together, our findings suggest that carcinogenic HPV-related CINs and cervical cancers are linked to a small, discrete cell population that localizes to the SC junction of the cervix, expresses a unique gene expression signature, and is not regenerated after excision. The findings in this study uncover a potential target for cervical cancer prevention, provide insight into the risk assessment of cervical lesions, and establish a model for elucidating the pathway to cervical cancer following carcinogenic HPV infection.
