Massive T-lymphocyte infiltration into the host stroma is essential for fibroblast growth factor-2-promoted growth and metastasis of mammary tumors via neovascular stability.

The American Journal of Pathology
Satoshi TsunodaIkuo Saiki

Abstract

Inflammation in the tumor stroma greatly influences tumor development. In the present study, we investigated the roles of fibroblast growth factor (FGF)-2-induced chronic inflammation in the development of 4T1 murine mammary tumors. Administration of FGF-2 into the tumor inoculation site during the initial phase of tumor growth enhanced tumor growth and pulmonary metastasis as well as microvessel density in tumor tissues in normal but not in nude mice. Infiltration of T lymphocytes and macrophages, recruitment of pericytes/vascular mural cells in neovascular walls, and the expression levels of cyclooxygenase (COX)-2 and vascular endothelial growth factor A (VEGFA) were also enhanced in the FGF-2-activated host stroma of normal mice. In addition, FGF-2-induced tumor growth and metastasis was abrogated by administration of either an immunosuppressant, FK506, or a COX-2 inhibitor. FGF-2 enhanced prostaglandin E(2) secretion in cultured T lymphocytes. In addition, VEGFA secretion was increased in a co-culture of T lymphocytes and fibroblasts in vitro. These results indicate that the massive infiltration of T lymphocytes into FGF-2-activated host stroma during the initial phase of tumor growth enhances neovascular stability by regul...Continue Reading

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Citations

Jan 1, 2011·BMJ Case Reports·Pedro CuevasGuillermo Giménez-Gallego
Feb 13, 2010·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Cristiane FuruseVera Cavalcanti de Araújo
Sep 22, 2010·Transplant International : Official Journal of the European Society for Organ Transplantation·Yekhtina ZhannaMichael Yechiel Shapira
Feb 13, 2014·Physiological Genomics·Brad RybinskiEdna Cukierman

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