blocking fibroblast growth factor receptor signaling inhibits tumor growth, lymphangiogenesis, and metastasis阻止纤维母细胞生长因子受体信号抑制肿瘤生长,lymphangiogenesis和转移.pdf

Blocking Fibroblast Growth Factor Receptor Signaling Inhibits Tumor Growth, Lymphangiogenesis, and Metastasis ´ ´ 1,2,3¤ 4 1,2 5 3,4 Frederic Larrieu-Lahargue , Alana L. Welm , Marion Bouchecareilh , Kari Alitalo , Dean Y. Li *, Andreas Bikfalvi1,2*, Patrick Auguste1,2 ` ´ 1 Laboratoire de l’Angiogenese et du Microenvironement des Cancers, Universite de Bordeaux, Talence, France, 2 INSERM U 1029, Talence, France, 3 Program in Molecular Medicine, University of Utah, Salt Lake City, Utah, United States of America, 4 Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, United States of America, 5 Molecular Cancer Biology Program, Biomedicum Helsinki, Department of Pathology, Haartman Institute and Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland Abstract Fibroblast Growth Factor receptor (FGFR) activity plays crucial roles in tumor growth and patient survival. However, FGF (Fibroblast Growth Factor) signaling as a target for cancer therapy has been under-investigated compared to other receptor tyrosine kinases. Here, we studied the effect of FGFR signaling inhibition on tumor growth, metastasis and lymphangiogenesis by expressing a dominant negative FGFR (FGFR-2DN) in an orthotopic mouse mammary 66c14 carcinoma model. We show that FGFR-2DN-expressing 66c14 cells proliferate in vitro slower than controls. 66c14 tumor outgrowth and lung metastatic foci are reduced in mice implanted with FGFR-2DN-expressing cells, which also exhibited b