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Fibroblast growth factor-2-induced host stroma reaction during initial tumor growth promotes progression of mouse melanoma via vascular endothelial growth factor A-dependent neovascularization
- Source :
- Cancer Science. 98:541-548
- Publication Year :
- 2007
- Publisher :
- Wiley, 2007.
-
Abstract
- 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.
- Subjects :
- Vascular Endothelial Growth Factor A
Cancer Research
Pathology
medicine.medical_specialty
Skin Neoplasms
Basic fibroblast growth factor
Melanoma, Experimental
Biology
Fibroblast growth factor
Antibodies
Metastasis
Neovascularization
Mice
chemistry.chemical_compound
Stroma
medicine
Animals
Neoplasm Metastasis
Glucocorticoids
Neovascularization, Pathologic
Melanoma
General Medicine
medicine.disease
Mice, Inbred C57BL
Vascular endothelial growth factor A
Oncology
chemistry
Tumor progression
Lymphatic Metastasis
Disease Progression
Cancer research
Female
Fibroblast Growth Factor 2
Stromal Cells
medicine.symptom
Neoplasm Transplantation
Subjects
Details
- ISSN :
- 13497006 and 13479032
- Volume :
- 98
- Database :
- OpenAIRE
- Journal :
- Cancer Science
- Accession number :
- edsair.doi.dedup.....95d19da41e55ec8ddf5caf58e2ef64b3