RRC ID 11842
Author Muramatsu M, Yamamoto S, Osawa T, Shibuya M.
Title Vascular endothelial growth factor receptor-1 signaling promotes mobilization of macrophage lineage cells from bone marrow and stimulates solid tumor growth.
Journal Cancer Res.
Abstract Vascular endothelial growth factor and its receptors, including Flt-1 and Flk-1, are involved in angiogenesis under physiologic and pathologic conditions. Recently, Flt-1-expressing cells were reported to contribute to the intracranial growth of glioma cells. However, the role of Flt-1 signaling in solid tumor growth in s.c. tissue has not been elucidated. To investigate how Flt-1 signaling is involved in the proliferation of solid tumors, we implanted tumor cells into wild-type (Wt) and Flt-1 tyrosine kinase (TK)-deficient (Flt-1 TK(-/-)) mice. Growth of HSML and B16 but not Lewis lung carcinoma cell in s.c. tissue was significantly decreased in Flt-1 TK(-/-) mice. Angiogenesis in HSML and B16 tumors was remarkably reduced in Flt-1 TK(-/-) mice. Moreover, the infiltration of macrophage lineage cells into HSML and B16 tumors was clearly suppressed in Flt-1 TK(-/-) mice. Pericyte marker(+) cells were also reduced in Flt-1 TK(-/-) mice. However, in the border area of tumor, angiogenesis and the infiltration of macrophage lineage cell were basically similar between Wt and Flt-1 TK(-/-) mice. In bone marrow (BM) transplantation experiments, tumor angiogenesis, infiltration of macrophage lineage cells, and tumor growth were significantly suppressed in Wt/Flt-1 TK(-/-) mice implanted with Flt-1 TK(-/-) BM cells compared with those implanted with Wt BM cells. We conclude that Flt-1 signaling is involved in the function of BM-derived cell, such as the migration of macrophages into cancerous tissues, and significantly contributes to angiogenesis and tumor progression.
Volume 70(20)
Pages 8211-21
Published 2010-10-15
DOI 10.1158/0008-5472.CAN-10-0202
PII 0008-5472.CAN-10-0202
PMID 20924106
MeSH Alternative Splicing Animals Bone Marrow Cells / pathology Bone Marrow Cells / physiology* Carcinoma, Lewis Lung / pathology Cell Division Cell Line, Tumor DNA Primers Female Fibroblast Growth Factor 2 / genetics Lung Neoplasms / pathology Macrophages / pathology Macrophages / physiology* Mice Mice, Knockout Neoplasms / pathology* Neovascularization, Pathologic / pathology* Receptor, Fibroblast Growth Factor, Type 1 / deficiency Receptor, Fibroblast Growth Factor, Type 1 / genetics Reverse Transcriptase Polymerase Chain Reaction Uterine Neoplasms / pathology Vascular Endothelial Growth Factor A / genetics Vascular Endothelial Growth Factor Receptor-1 / physiology*
IF 8.378
Times Cited 49
Mice C57BL/6-Tg(CAG-EGFP)C14-Y01-FM131Osb