| Literature DB >> 24631293 |
Junko Inagaki1, Katsuyuki Takahashi1, Hiroko Ogawa1, Keiichi Asano1, Omer Faruk Hatipoglu1, Mehmet Zeynel Cilek1, Masanari Obika1, Takashi Ohtsuki1, Matthias Hofmann2, Shozo Kusachi3, Yoshifumi Ninomiya1, Satoshi Hirohata4.
Abstract
Angiogenesis and lymphangiogenesis play roles in malignant tumor progression, dissemination, and metastasis. ADAMTS1, a member of the matrix metalloproteinase family, is known to inhibit angiogenesis. Recombinant ADAMTS1 was shown to strongly inhibit angiogenesis. We investigated whether ADAMTS1 inhibited lymphangiogenesis in the present study. We examined cell proliferation and cell migration in normal human dermal lymphatic microvascular endothelial cells (HMVEC-dLy) transduced with or without adenoviral human ADAMTS1 gene therapy. We then examined the VEGFC/VEGFR3 signal transduction pathway in ADAMTS1-transduced HMVEC-dLy. Cell proliferation and tube formation in Matrigel were significantly lower with transduced ADAMTS1 than with control (non-transduced HMVEC-dLy). The phosphorylation of VEGFR3 was also attenuated by ADAMTS1 gene therapy in HMVEC-dLy. Immunoprecipitation assays revealed that ADAMTS1 formed a complex with VEGFC. Our results demonstrated that ADAMTS1 inhibited lymphangiogenesis in vitro. The data highlight the new function of ADAMTS1 in the regulation of lymphangiogenesis and the therapeutic potential of ADAMTS1 in cancer therapy.Entities:
Keywords: ADAMTS1; Lymphangiogenesis; Lymphatic endothelial cell; VEGFC; VEGFR-3
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Year: 2014 PMID： 24631293 DOI： 10.1016/j.yexcr.2014.03.002
Source DB: PubMed Journal: Exp Cell Res ISSN： 0014-4827 Impact factor: 3.905