Host-related carcinoembryonic antigen cell adhesion molecule 1 promotes metastasis of colorectal cancer

被引：37

作者：

Arabzadeh, A. ^{[1
]}

Chan, C. ^{[1
,2
]}

Nouvion, A-L ^{[1
]}

Breton, V. ^{[1
]}

Benlolo, S. ^{[1
]}

DeMarte, L. ^{[1
]}

Turbide, C. ^{[1
]}

Brodt, P. ^{[2
,3
]}

Ferri, L. ^{[2
,3
]}

Beauchemin, N. ^{[1
,3
,4
,5
]}

机构：

[1] McGill Univ, Goodman Canc Res Ctr, Montreal, PQ H3G 1Y6, Canada

[2] McGill Univ, Dept Surg, Montreal, PQ H3G 1Y6, Canada

[3] McGill Univ, Dept Oncol, Montreal, PQ H3G 1Y6, Canada

[4] McGill Univ, Dept Med, Montreal, PQ H3G 1Y6, Canada

[5] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada

来源：

ONCOGENE | 2013年 / 32卷 / 07期

关键词：

CEACAM; 1; metastasis; microenvironment; intravital microscopy; MDSC; colorectal cancer; BILIARY GLYCOPROTEIN; TUMOR PROGRESSION; PROSTATE-CANCER; POSSIBLE ROLES; CEACAM1; EXPRESSION; CD66A; ANGIOGENESIS; APOPTOSIS; INVASION;

D O I：

10.1038/onc.2012.112

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Liver metastasis is the predominant cause of colorectal cancer (CRC)-related mortality in developed countries. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a cell adhesion molecule with reduced expression in early phases of CRC development and thus functions as a tumor growth inhibitor. However, CEACAM1 is upregulated in metastatic colon cancer, suggesting a bimodal role in CRC progression. To investigate the role of this protein in the host metastatic environment, Ceacam1(-/-) mice were injected intrasplenically with metastatic MC38 mouse CRC cells. A significant reduction in metastatic burden was observed in Ceacam1(-/-) compared with wild-type (WT) livers. Intravital microscopy showed decreased early survival of MC38 cells in Ceacam1(-/-) endothelial environment. Metastatic cell proliferation within the Ceacaml-i- livers was also diminished. Bone marrow-derived cell recruitment, attenuation of immune infiltrates and diminished CCL2, CCL3 and CCL5 chemokine production participated in the reduced Ceacam1(-/-) metastatic phenotype. Transplantations of WT bone marrow (BM) into Ceacam1(-/-) mice fully rescued metastatic development, whereas Ceacam1(-/-) BM transfer into WT mice showed reduced metastatic burden. Chimeric immune cell profiling revealed diminished recruitment of CD11b(+) Gr1(+) myeloid-derived suppressor cells (MDSCs) to Ceacam1(-/-)metastatic livers and adoptive transfer of MDSCs confirmed the involvement of these immune cells in reduction of liver metastasis. CEACAM1 may represent a novel metastatic CRC target for treatment. Oncogene (2013) 32, 849-860; doi:10.1038/onc.2012.112; published online 2 April 2012

引用

页码：849 / 860

页数：12

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