基于PDB文件2a4c并利用PyMOL構(gòu)建出鈣粘附蛋白-11(cadherin-11)結(jié)構(gòu)圖,，圖片來自維基共享資源,。
腫瘤轉(zhuǎn)移導(dǎo)致90%癌癥病人死亡,。理解這種過程的作用機(jī)制是癌癥研究的首要目標(biāo)之一,。腫瘤轉(zhuǎn)移過程涉及一系列連接在一起的步驟,，從而使得原發(fā)性腫瘤侵襲周圍組織,，最終在全身擴(kuò)散,。腫瘤發(fā)生轉(zhuǎn)移時(shí)侵襲的首批組織之一就是腫瘤周圍的淋巴結(jié)。
來自西班牙Bellvitge生物醫(yī)學(xué)研究所(Bellvitge Biomedical Research Institute)的研究人員Manel Esteller領(lǐng)導(dǎo)的一個(gè)研究小組在Journal of Pathology期刊上發(fā)表一篇研究論文,。他們鑒定出一種解釋癌細(xì)胞如何從原始腫瘤位點(diǎn)遷移至淋巴結(jié)的機(jī)制,。這項(xiàng)研究已揭示在黑素瘤和頭頸部腫瘤(head and neck tumour)病人淋巴結(jié)中生長的轉(zhuǎn)移瘤細(xì)胞(metastatic tumour cell)喪失鈣粘附蛋白-11(cadherin-11)活性。
這種蛋白的正常功能是作為一種錨將細(xì)胞固定在特定位點(diǎn)并阻止它們運(yùn)動(dòng),。鈣粘附蛋白-11基因失活導(dǎo)致這種固定作用丟失從而使得腫瘤細(xì)胞“跳躍”到相鄰器官和諸如淋巴結(jié)之類的組織結(jié)構(gòu),。
這項(xiàng)研究還提出這種腫瘤轉(zhuǎn)移過程能夠被逆轉(zhuǎn)，因?yàn)樵隗w內(nèi)和體外模型中,，恢復(fù)鈣粘附蛋白-11的活性能夠延緩腫瘤生長并降低產(chǎn)生轉(zhuǎn)移瘤的能力,。不過這種逆轉(zhuǎn)性能還需要在臨床試驗(yàn)中進(jìn)行進(jìn)一步研究，但是它為研究腫瘤轉(zhuǎn)移的生物學(xué)特征和如何進(jìn)行治療性應(yīng)用提供一個(gè)大有希望的起點(diǎn),。(生物谷：towersimper編譯)
doi:10.1002/path.4011
PMC:
PMID:
Epigenetic Disruption of Cadherin-11 in Human Cancer Metastasis
F. Javier Carmona, Alberto Villanueva, August Vidal, Clara Muñoz, Sara Puertas, Rosa M. Penin, Montserrat Gomà, Amaia Lujambio, Josep M Piulats, Ricard Mesía, Montse Sánchez-Céspedes, Manel Manós, Enric Condom, Suzanne A. Eccles, Manel Esteller
The immune system protects from infections primarily by detecting and eliminating the invading pathogens; however, the host organism can also protect itself from infectious diseases by reducing the negative impact of infections on host fitness. This ability to tolerate a pathogen’s presence is a distinct host defense strategy, which has been largely overlooked in animal and human studies. Introduction of the notion of “disease tolerance” into the conceptual tool kit of immunology will expand our understanding of infectious diseases and host pathogen interactions. Analysis of disease tolerance mechanisms should provide new approaches for the treatment of infections and other diseases.
