Abrogation of TGFβ signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis
Abrogation of TGFβ signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis
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DOI：
10.1016/j.ccr.2007.12.004
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发表时间：
2008-01-01
期刊：
影响因子：
50.3
通讯作者：
Mosesl, Harold L.
中科院分区：
文献类型：
--
作者：
Yang, Li;Huang, Jianhua;Mosesl, Harold L.
异常的 TGF β 信号传导在人类癌症中很常见，并导致肿瘤转移。在这里，我们证明了Gr-1+CD11b+骨髓细胞被招募到II型TGFβ受体基因（Tgfbr2）缺失的乳腺癌中并直接促进肿瘤转移。 Gr-1+CD11b+细胞浸润到肿瘤组织的侵袭前沿，通过金属蛋白酶活性的过程促进肿瘤细胞的侵袭和转移。 Gr-1+CD11b+ 细胞的这种浸润也会导致 Tgfbr2 缺失的肿瘤中 TGF beta 1 的丰度增加。 Gr-1+CD11b+ 细胞招募到 Tgfbr2 缺失的肿瘤中涉及两个趋化因子受体轴，即 SDF-1/CXCR4 和 CXCL5/CXCR2 轴。总之，这些数据表明 Gr-1+CD11b+ 细胞通过增强肿瘤细胞侵袭和转移来促进 TGFβ 介导的转移。
Aberrant TGF beta signaling is common in human cancers and contributes to tumor metastasis. Here, we demonstrate that Gr-1+CD11b+ myeloid cells are recruited into mammary carcinomas with type II TGF beta receptor gene (Tgfbr2) deletion and directly promote tumor metastasis. Gr-1+CD11b+ cells infiltrate into the invasive front of tumor tissues and facilitate tumor cell invasion and metastasis through a process involving metalloproteinase activity. This infiltration of Gr-1+CD11b+ cells also results in increased abundance of TGF beta 1 in tumors with Tgfbr2 deletion. The recruitment of Gr-1+CD11b+ cells into tumors with Tgfbr2 deletion involves two chemokine receptor axes, the SDF-1/CXCR4 and CXCL5/CXCR2 axes. Together, these data indicate that Gr-1+CD11b+ cells contribute to TGF beta-mediated metastasis through enhancing tumor cell invasion and metastasis.