Open AccessFibroblast growth factor‐2‐induced host stroma reaction during initial tumor growth promotes progression of mouse melanoma via vascular endothelial growth factor A‐dependent neovascularization
Author(s) -
Tsunoda Satoshi,
Nakamura Toshiyuki,
Sakurai Hiroaki,
Saiki Ikuo
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00432.x
Subject(s) - stroma , neovascularization , vascular endothelial growth factor , cancer research , growth factor , fibroblast growth factor , melanoma , vascular endothelial growth factor c , angiogenesis , basic fibroblast growth factor , vascular endothelial growth factor a , biology , pathology , microbiology and biotechnology , immunology , medicine , vegf receptors , immunohistochemistry , receptor
Fibroblast growth factor (FGF)‐2 has been considered to play a critical role in neovascularization in several tumors; however, its precise role in tumor progression is not fully understood. In the present study, we have characterized the role of FGF‐2 in B16‐BL6 mouse melanoma cells, focusing on effects during the initial phase of tumor growth. FGF‐2 was injected at the tumor inoculation site of dorsal skin during the initial phase. FGF‐2 induced marked tumor growth and lymph node metastasis. This was well correlated with an increase in neovascularization in the host stroma. FGF‐2 also recruited inflammatory and mesenchymal cells in host stroma. Marked tumor growth, pulmonary metastasis and intensive neovascularization in tumor parenchyma were also observed after a single injection of FGF‐2 into the footpad inoculation site. In contrast, repeated injections of FGF‐2 at a site remote from the footpad tumor were ineffective in promoting tumor growth and metastasis. These promoting activities of FGF‐2 were blocked by local injections of a glucocorticoid hormone, suggesting that host inflammatory responses induced by FGF‐2 are associated with FGF‐2‐induced tumor progression. In addition, although FGF‐2 did not promote cellular proliferation and vascular endothelial growth factor A (VEGFA) mRNA expression in B16‐BL6 cells in vitro , FGF‐2 induced VEGFA expression in host stroma rather than tumor tissue, and local injections of a neutralizing antibody against VEGFA inhibited these activities of FGF‐2 in vivo . These results indicate that abundant FGF‐2 during the initial phase of tumor growth induces VEGFA‐dependent intensive neovascularization in host stroma, and supports marked tumor growth and metastasis. ( Cancer Sci 2007; 98: 541–548)