Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis

作者：Yang Li^*; Huang Jianhua; Ren Xiubao; Gorska Agnieszka E; Chytil Anna; Aakre Mary; Carbone David P; Matrisian Lynn M; Richmond Ann; Lin P Charles; Mosesl Harold L

来源：Cancer Cell, 2008, 13(1): 23-35.

DOI：10.1016/j.ccr.2007.12.004

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.

• 出版日期2008-1