Tumor angiogenesis mediated by myeloid cells is negatively regulated by CEACAM1.
Tumor angiogenesis mediated by myeloid cells is negatively regulated by CEACAM1.
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由CEACAM1负调控髓样细胞介导的肿瘤血管生成。
DOI：
10.1158/0008-5472.can-11-3016
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发表时间：
2012-05-01
期刊：
影响因子：
11.2
通讯作者：
Shively JE
中科院分区：
文献类型：
--
作者：
Lu R;Kujawski M;Pan H;Shively JE
Bv8 (prokineticin 2) expressed by Gr1+CD11b+ myeloid cells is critical for VEGF-independent tumor angiogenesis. Although G-CSF has been shown to be a key inducer of Bv8 expression, the basis for Bv8 production in driving tumor angiogenesis is undefined. Since the cell adhesion molecule CEACAM1 that is highly expressed on Gr1+CD11b+ myeloid cells is known to regulate G-CSFR signaling, we hypothesized that CEACAM1 would regulate Bv8 production in these cells. In support of this hypothesis we found that Bv8 expression was elevated in Gr1+CD11b+ cells from Ceacam1-deficient mice implanted with B16 melanoma, increasing the infiltration of Gr1+CD11b+ myeloid cells in melanoma tumors and enhancing their growth and angiogenesis. Further, treatment with anti-Gr1 or anti-Bv8 or anti-G-CSF monoclonal antibody reduced myeloid cell infiltration, tumor growth, and angiogenesis to levels observed in tumor bearing wild-type mice. Reconstitution of CEACAM1-deficient mice with wild type bone marrow cells restored tumor infiltration of Gr1+CD11b+ cells along with tumor growth and angiogenesis. Treatment of tumor bearing wild-type mice with anti-CEACAM1 antibody limited tumor outgrowth and angiogenesis, albeit to a lesser extent. Tumor growth in Ceacam1-deficient mice was not affected significantly in Rag−/− background, indicating that CEACAM1 expression in T- and B-lymphocytes had a negligible role in this pathway. Together, our findings demonstrate that CEACAM1 negatively regulates Gr1+CD11b+ myeloid cell dependent tumor angiogenesis by inhibiting the G-CSF-Bv8 signaling pathway.
