轉(zhuǎn)移發(fā)生時(shí)腫瘤細(xì)胞通過(guò)血液“移植”到其他器官?？茖W(xué)家已經(jīng)發(fā)現(xiàn)腫瘤細(xì)胞從血管侵入組織的伎倆：腫瘤細(xì)胞產(chǎn)生信號(hào)蛋白使動(dòng)脈壁通透性增加,，從而清除他們到達(dá)不同的器官的通路。最新研究結(jié)果發(fā)表在本期的Cancer Cell雜志上,。
一個(gè)腫瘤細(xì)胞是如何建立一個(gè)信號(hào)通路來(lái)便于自身轉(zhuǎn)移的呢,？慕尼黑工業(yè)大學(xué)Klinikum rechts der Isar和 Helmholtz Zentrum München科學(xué)家們通過(guò)研究結(jié)腸癌在這一領(lǐng)域取得了重大發(fā)現(xiàn)。他們了解到腫瘤細(xì)胞釋放趨化因子,。在轉(zhuǎn)移性結(jié)腸癌細(xì)胞中,，所釋放的趨化因子是CCL2。CCL2趨化因子與血管壁（內(nèi)皮細(xì)胞）相結(jié)合,，激活相應(yīng)的受體（CCR2受體）,。使得內(nèi)皮細(xì)胞的滲透 性增加，便于腫瘤細(xì)胞轉(zhuǎn)移,。
Mathias Heikenwälder教授解釋說(shuō)：腫瘤細(xì)胞遷移過(guò)程中采用一個(gè)聰明的伎倆即腫瘤細(xì)胞接受健康細(xì)胞所發(fā)出的信號(hào)與內(nèi)皮細(xì)胞相互作用,。迄今為止，研究主要集中在腫瘤趨化因子募集巨噬細(xì)胞,。通過(guò)理解趨化因子受體與血管內(nèi)皮細(xì)胞的作用,，我們有可能發(fā)現(xiàn)一個(gè)全新的方法來(lái)治療癌癥。
測(cè)量趨化因子的數(shù)量,，可以讓我們預(yù)測(cè)原發(fā)腫瘤蔓延到其他器官以及預(yù)測(cè)患者轉(zhuǎn)移的風(fēng)險(xiǎn),，此外，阻斷血管內(nèi)皮細(xì)胞的趨化因子受體CCR2可能為醫(yī)療專(zhuān)業(yè)人員提供了新的治療方式,。
在他們的研究中,，科學(xué)家使用了結(jié)腸癌組織和結(jié)腸癌的小鼠和人類(lèi)細(xì)胞株。接下來(lái)的步驟將研究結(jié)果如何擴(kuò)展到其他類(lèi)型的癌癥上,。（生物谷：Bioon.com）
doi:10.1016/j.ccr.2012.05.023
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Endothelial CCR2 Signaling Induced by Colon Carcinoma Cells Enables Extravasation via the JAK2-Stat5 and p38MAPK Pathway
Monika Julia Wolf, Alexandra Hoos, Judith Bauer, Steffen Boettcher, Markus Knust, Achim Weber, Nicole Simonavicius, Christoph Schneider, Matthias Lang, Michael Stürzl, Roland S. Croner, Andreas Konrad, Markus G. Manz, Holger Moch, Adriano Aguzzi, Geert van Loo, Manolis Pasparakis, Marco Prinz, Lubor Borsig, Mathias Heikenwalder
Increased expression of the chemokine CCL2 in tumor cells correlates with enhanced metastasis, poor prognosis, and recruitment of CCR2+Ly6Chi monocytes. However, the mechanisms driving tumor cell extravasation through the endothelium remain elusive. Here, we describe CCL2 upregulation in metastatic UICC stage IV colon carcinomas and demonstrate that tumor cell-derived CCL2 activates the CCR2+ endothelium to increase vascular permeability in vivo. CCR2 deficiency prevents colon carcinoma extravasation and metastasis. Of note, CCR2 expression on radio-resistant cells or endothelial CCR2 expression restores extravasation and metastasis in Ccr2/ mice. Reduction of CCR2 expression on myeloid cells decreases but does not prevent metastasis. CCL2-induced vascular permeability and metastasis is dependent on JAK2-Stat5 and p38MAPK signaling. Our study identifies potential targets for treating CCL2-dependent metastasis.
