乳腺癌是女性排名第一的常見惡性腫瘤，其癌細胞轉移是引起患者死亡的主要原因,。目前的研究正在進一步闡明癌癥轉移的限速步驟,，比如循環(huán)腫瘤細胞的外滲及侵襲。
血管緊張素II是一種主要的血管活性肽,，它局部產(chǎn)生并釋放到血液,。近日，法國巴黎科尚研究所的研究人員著手完成了一項有意義的研究,，他們發(fā)現(xiàn)血管緊張素II能夠促進癌細胞遷移,。
在該研究中,，他們使用了一個癌癥轉移的體內(nèi)模型。為了研究癌細胞轉移的重要步驟,，他們將能夠穩(wěn)定產(chǎn)生熒光的乳腺癌細胞系(D3H2LN)注入到裸鼠,。通過實時活體影像學研究，他們發(fā)現(xiàn)血管緊張素II促進了轉移灶的形成,。
實驗發(fā)現(xiàn),，用這種多肽預處理后，發(fā)生癌細胞轉移的老鼠數(shù)量增加,，并且每個老鼠體內(nèi)的轉移瘤的數(shù)量及大小也相應的增加和增大,。在體外，血管緊張素II通過促進癌細胞黏附于內(nèi)皮細胞,、跨內(nèi)皮遷移并通過細胞外基質,，促進了癌癥轉移。
在分子水平,，由DNA微陣列分析表明,，血管緊張素II預處理后共有102個基因差異性表達,。血管緊張素II調控了兩類與其前體血管緊張素原緊密相關的基因,。在這些基因中，MMP2/MMP9和ICAM1M的上調表達跟由參與細胞黏附,、遷移及侵襲的基因組成的網(wǎng)絡相關聯(lián),。
這些結果表明，靶向血管緊張素II可能會成為抑制浸潤性乳腺癌轉移的有效策略,。相關論文發(fā)表在4月20日的PLoS ONE,。（生物谷Deepblue編譯）
doi: 10.1371/journal.pone.0035667
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Angiotensin II Facilitates Breast Cancer Cell Migration and Metastasis
Sylvie Rodrigues-Ferreira, Mohamed Abdelkarim, Patricia Dillenburg-Pilla, Anny-Claude Luissint, Anne di-Tommaso, Frédérique Deshayes, Carmen Lucia S. Pontes, Angie Molina, Nicolas Cagnard, Franck Letourneur, Marina Morel, Rosana I. Reis, Dulce E. Casarini, Benoit Terris, Pierre-Olivier Couraud, Claudio M. Costa-Neto, Mélanie Di Benedetto, Clara Nahmias.
Breast cancer metastasis is a leading cause of death by malignancy in women worldwide. Efforts are being made to further characterize the rate-limiting steps of cancer metastasis, i.e. extravasation of circulating tumor cells and colonization of secondary organs.In this study, we investigated whether angiotensin II, a major vasoactive peptide both produced locally and released in the bloodstream, may trigger activating signals that contribute to cancer cell extravasation and metastasis.We used an experimental in vivo model of cancer metastasis in which bioluminescent breast tumor cells (D3H2LN) were injected intra-cardiacally into nude mice in order to recapitulate the late and essential steps of metastatic dissemination. Real-time intravital imaging studies revealed that angiotensin II accelerates the formation of metastatic foci at secondary sites.Pre-treatment of cancer cells with the peptide increases the number of mice with metastases, as well as the number and size of metastases per mouse. In vitro, angiotensin II contributes to each sequential step of cancer metastasis by promoting cancer cell adhesion to endothelial cells, trans-endothelial migration and tumor cell migration across extracellular matrix.At the molecular level, a total of 102 genes differentially expressed following angiotensin II pre-treatment were identified by comparative DNA microarray. Angiotensin II regulates two groups of connected genes related to its precursor angiotensinogen.
