在這個(gè)表皮表層里，可見(jiàn)朗格漢斯細(xì)胞（綠色）構(gòu)成一個(gè)細(xì)胞網(wǎng)絡(luò),，延長(zhǎng)樹(shù)突狀的進(jìn)程
日前，刊登在最新一期Science上的一篇論文"Langerhans Cells Facilitate Epithelial DNA Damage and Squamous Cell Carcinoma"表明,，以能探測(cè)到皮膚中的外來(lái)入侵物而聞名的一組免疫細(xì)胞也能通過(guò)代謝環(huán)境中的化學(xué)物質(zhì)而促進(jìn)腫瘤的生長(zhǎng),。
包括皮膚及那些覆蓋許多身體表面的上皮組織形成抵御微生物及可以引起癌癥的化學(xué)毒素的關(guān)鍵性的屏障。 （在人類(lèi)中，90%的癌癥起源于上皮組織,。） 這些組織常常充滿(mǎn)了樹(shù)突狀細(xì)胞,，其中包括一個(gè)叫做朗格漢斯細(xì)胞的亞組細(xì)胞，這些細(xì)胞可識(shí)別抗原并將它們“穿戴”在其表面以警示T細(xì)胞進(jìn)行防御反應(yīng),。 這些抗原可以是微生物,，或它們也可來(lái)自腫瘤。
然而,，令人感到驚訝的是,，缺乏朗格漢斯細(xì)胞的小鼠則可不受化學(xué)性致癌作用的侵害，而B(niǎo)adri Modi 及其同事希望能找出其原因,。 他們?nèi)缃裼靡环N鱗狀細(xì)胞癌的小鼠模型揭示了朗格漢斯細(xì)胞可驅(qū)使健康的皮膚細(xì)胞轉(zhuǎn)變成為癌性細(xì)胞,。 朗格漢斯細(xì)胞在對(duì)致癌物7,12 二甲基苯丙蒽 (DMBA) 進(jìn)行回應(yīng)時(shí)會(huì)增加其對(duì)某種叫做CYP1B1酶的表達(dá)，這種酶會(huì)將DMBA代謝成為一種可誘導(dǎo)細(xì)胞內(nèi)突變的化合物,。
文章的作者指出,，DMBA是一種聚芳烴，或PAH,，而這些烴類(lèi)化合物一般在工業(yè)污染中非常普遍,。 他們說(shuō)，含有PAH的顆粒物質(zhì)可能是人類(lèi)皮膚癌中的一種未得到正確評(píng)價(jià)的環(huán)境因素,。（生物谷bioon.com）
doi:10.1126/science.1211600
PMC:
PMID:
Langerhans Cells Facilitate Epithelial DNA Damage and Squamous Cell Carcinoma
Badri G. Modi1,*, Jason Neustadter1,*, Elisa Binda8,9, Julia Lewis1, Renata B. Filler1, Scott J. Roberts1, Bernice Y. Kwong1, Swapna Reddy1, John D. Overton3, Anjela Galan1, Robert Tigelaar1, Lining Cai4, et al.
Polyaromatic hydrocarbons (PAHs) are prevalent, potent carcinogens, and 7,12-dimethylbenz[a]anthracene (DMBA) is a model PAH widely used to study tumorigenesis. Mice lacking Langerhans cells (LCs), a signatory epidermal dendritic cell (DC), are protected from cutaneous chemical carcinogenesis, independent of T cell immunity. Investigation of the underlying mechanism revealed that LC-deficient skin was relatively resistant to DMBA-induced DNA damage. LCs efficiently metabolized DMBA to DMBA-trans-3,4-diol, an intermediate proximal to oncogenic Hras mutation, and DMBA-treated LC-deficient skin contained significantly fewer Hras mutations. Moreover, DMBA-trans-3,4-diol application bypassed tumor resistance in LC-deficient mice. Additionally, the genotoxic impact of DMBA on human keratinocytes was significantly increased by prior incubation with human-derived LC. Thus, tissue-associated DC can enhance chemical carcinogenesis via PAH metabolism, highlighting the complex relation between immune cells and carcinogenesis.
