最新調(diào)查數(shù)據(jù)顯示,，平均每3分鐘世界上就有一位婦女被診斷為乳腺癌,，我國(guó)女性乳腺癌的發(fā)病率和死亡率也是逐年上升，乳腺癌已經(jīng)成為要挾女性健康的“頭號(hào)殺手”,。乳腺癌細(xì)胞的轉(zhuǎn)移是其致死的主要原因,。乳腺癌細(xì)胞之所以發(fā)生轉(zhuǎn)移，除了癌細(xì)胞本身的因素外,，還跟癌細(xì)胞周圍的非可控性炎癥反應(yīng)有關(guān),。非可控性炎癥在癌癥的發(fā)生發(fā)展進(jìn)程中扮演著十分重要的角色。尤為重要的是,，非可控性炎性和惡性腫瘤之間所形成的調(diào)控網(wǎng)絡(luò),，涉及眾多的基因或蛋白質(zhì),、非編碼RNA和代謝小分子等各種分子元件，彼此間通過(guò)復(fù)雜的相互作用形成多維的和動(dòng)態(tài)的“互聯(lián)網(wǎng)”,。因此,，分析非可控性炎癥與惡性腫瘤相互作用的動(dòng)態(tài)調(diào)控網(wǎng)絡(luò)在惡性腫瘤發(fā)生發(fā)展中的作用是一個(gè)十分重要的科學(xué)問(wèn)題。
近幾年來(lái),，宋爾衛(wèi)教授帶領(lǐng)的研究團(tuán)隊(duì)在國(guó)家自然科學(xué)基金重點(diǎn)項(xiàng)目,、杰出青年基金項(xiàng)目和科技部“973”項(xiàng)目等的支持下，對(duì)非可控性炎癥在乳腺癌中的作用進(jìn)行了深入研究,。發(fā)現(xiàn)了乳腺癌組織中一個(gè)重要的非可控性炎癥因素,，即腫瘤相關(guān)巨噬細(xì)胞（Tumor-Associated Macrophages，TAM）可以通過(guò)分泌炎癥因子CCL18促進(jìn)乳腺癌細(xì)胞的浸潤(rùn)和轉(zhuǎn)移,，乳腺癌組織中分泌CCL18的TAM越多,，乳腺癌病人發(fā)生淋巴結(jié)和器官轉(zhuǎn)移的機(jī)率就越大，預(yù)后就越差,。干預(yù)了TAM對(duì)CCL18的分泌能明顯抑制乳腺癌細(xì)胞的轉(zhuǎn)移。不僅如此,，CCL18是目前為數(shù)不多的尚未發(fā)現(xiàn)相應(yīng)受體的炎癥因子,，對(duì)其受體認(rèn)識(shí)的缺失一直制約了醫(yī)學(xué)界針對(duì)CCL18的治療策略。中山大學(xué)宋爾衛(wèi)團(tuán)隊(duì)和中國(guó)科技大學(xué)生命科學(xué)院姚雪彪團(tuán)隊(duì)共同努力攻關(guān),，分離并鑒定了CCL18的受體是一個(gè)新型的六次跨膜蛋白PITPNM3,，而非傳統(tǒng)的七次跨膜蛋白。通過(guò)阻斷或沉默該受體,可以達(dá)到逆轉(zhuǎn)CCL18對(duì)乳腺癌細(xì)胞轉(zhuǎn)移的促進(jìn)作用,。該研究開(kāi)辟了一條從非可控性炎癥著手抑制乳腺癌轉(zhuǎn)移的途徑,，找到了CCL18與乳腺癌相互作用的節(jié)點(diǎn)——CCL18的受體膜蛋白PITPNM3，為進(jìn)一步針對(duì)該節(jié)點(diǎn)靶向控制非可控性炎癥,，開(kāi)發(fā)用于治療腫瘤的治療性抗體和小分子化合物奠定了基礎(chǔ),。此項(xiàng)研究成果于2011年4月12日以Featured Article形式發(fā)表在知名國(guó)際科學(xué)期刊《Cancer Cell》（Cancer Cell, 2011，19（4）：541-555）,，此刊為Cell期刊系列,，影響因子IF為25.288）。同期還發(fā)表了國(guó)際著名學(xué)者Alberto Mantovani教授及其同事對(duì)這項(xiàng)研究成果意義的評(píng)述,，認(rèn)為這項(xiàng)研究工作進(jìn)一步闡述了趨化因子在腫瘤中的作用,，并認(rèn)為這個(gè)發(fā)現(xiàn)在腫瘤預(yù)后評(píng)估中具有重要意義，而且利用趨化因子治療腫瘤的策略已進(jìn)入臨床評(píng)估階段,。（生物谷Bioon.com）
生物谷推薦原文出處：
Cancer Cell, doi:10.1016/j.ccr.2011.02.006
CCL18 from Tumor-Associated Macrophages Promotes Breast Cancer Metastasis via PITPNM3
Jingqi Chen, Yandan Yao, Chang Gong, Fengyan Yu, Shicheng Su, Jianing Chen, Bodu Liu, Hui Deng, Fengsong Wang, Ling Lin, Herui Yao, Fengxi Su, Karen S. Anderson, Qiang Liu, Mark E. Ewen, Xuebiao Yao, Erwei Song
Highlights
CCL18 is abundantly produced in breast TAMs
CCL18 is associated with metastasis and poor prognosis of patients with breast cancer
CCL18 promotes invasion and metastasis of breast cancer cells
PITPNM3 is a receptor for CCL18 in promoting metastasis
Summary
Tumor-associated macrophages (TAMs) can influence cancer progression and metastasis, but the mechanism remains unclear. Here, we show that breast TAMs abundantly produce CCL18, and its expression in blood or cancer stroma is associated with metastasis and reduced patient survival. CCL18 released by breast TAMs promotes the invasiveness of cancer cells by triggering integrin clustering and enhancing their adherence to extracellular matrix. Furthermore, we identify PITPNM3 as a functional receptor for CCL18 that mediates CCL18 effect and activates intracellular calcium signaling. CCL18 promotes the invasion and metastasis of breast cancer xenografts, whereas suppressing PITPNM3 abrogates these effects. These findings indicate that CCL18 derived from TAMs plays a critical role in promoting breast cancer metastasis via its receptor, PITPNM3.
