In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 786-786
Kurzfassung:
Gr1+CD11b+ myeloid cells promote tumor angiogenesis and are refractory to VEGF antibodies treatment. Bv8, also known as Prokineticin 2, expressed in Gr1+CD11b+ cells and positively regulated by granulocyte colony-stimulating factor (G-CSF), has recently been shown to modulate Gr1+CD11b+ cells mobilization and tumor angiogenesis. Anti-Bv8 treatment reduced angiogenesis and growth. However, the signaling pathways in Gr1+CD11b+ to promote tumor angiogenesis are not fully understood. Carcinoembryonic antigen-related cell adhesion moclecule-1(CEACAM1) is highly expressed on Gr1+ myeloid cells, however the role of CEACAM1 in myeloid cells mediated tumor angiogenesis has not been investigated. We have demonstrated that tumor growth and angiogenesis was significantly enhanced in Ceacam1−/− mice, which was independent on T and B cells by backcrossing Ceacam1−/− mice with Rag1−/− mice. Meanwhile Gr1+CD11b+ cells infiltration in tumor, spleen and blood was increased. Tumors coinjected with Gr1+CD11b+ cells from Ceacam1−/− mice exhibited increased angiogenesis compared to coinjection with Gr1+CD11b+ cells from control mice. Depletion of Gr1+ cells inhibited tumor growth and angiogenesis in control and Ceacam1−/− mice. Gr1+CD11b+ cells from Ceacam1−/− mice expressed much higher Bv8 in vitro and in vivo. Further we have shown that CEACAM1 recruited Src-homology-phosphatase-1 (SHP-1) to attenuate granulocyte colony-stimulating factor receptor (G-CSFR)-Bv8 pathway in myeloid cells. Reconsititution of CEACAM1 into Ceacam1−/− bone marrow cells restored tumor growth and angiogenesis to normal level, and mutations of immunoreceptor tyrosine-based inhibitory motifs ITIMs abolished this restoration. Therefore, we identified CEACAM1, as an inhibitory regulator of G-CSFR-Bv8 pathway, negatively regulates myeloid cells dependent tumor angiogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 786. doi:10.1158/1538-7445.AM2011-786
Materialart:
Online-Ressource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2011-786
Sprache:
Englisch
Verlag:
American Association for Cancer Research (AACR)
Publikationsdatum:
2011
ZDB Id:
2036785-5
ZDB Id:
1432-1
ZDB Id:
410466-3
