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S1P Induces Lymphangiogenesis Through a MMP‐2/FGFR‐1‐dependent Pathway in Human Umbilical Vein Endothelial Cells
Author(s) -
Chang Chihao,
Lin Chihhsin,
Lin ChuanEn,
Chiang Chiling,
Lee Hsinyu
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1091.3
Subject(s) - lymphangiogenesis , angiogenesis , microbiology and biotechnology , lymphatic endothelium , sphingosine 1 phosphate , umbilical vein , vascular endothelial growth factor c , cancer research , sphingosine , receptor , chemistry , biology , vascular endothelial growth factor a , metastasis , lymphatic system , vascular endothelial growth factor , in vitro , cancer , immunology , vegf receptors , biochemistry , genetics
Lymphangiogenesis is an essential process in regulating tumor growth and metastasis. However, the molecular mechanisms regulating lymphangiogenesis are poorly understood. Sphingosine 1‐phosphate (S1P) is a potent bioactive phospholipid, which acts as a ligand for a family of G protein‐coupled S1P receptors. Through binding to these receptors, S1P modulates multiple biological processes, including cell proliferation and differentiation, inflammatory responses, and angiogenesis. Previous reports have shown that S1P induces lymphangiogenesis both in vitro and in vivo . In our present study, we demonstrated that S1P induces VEGF‐C expression and further upregulates lymphatic markers expression in human umbilical vein endothelial cells (HUVECs). Moreover, by using FGFR‐1 and MMP‐2 siRNA, we demonstrated that S1P induced HUVECs lymphangiogenesis is clarified through a MMP‐2/FGFR‐1 dependent pathway. Furthermore, S1P transactivates FGFR‐1 instead of enhancing FGFR‐1 expression. Based on the results, we concluded that S1P is an important regulator for lymphangiogenesis processes.