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Neuronal system‐derived calcitonin gene‐related peptide regulates angiogenesis in vivo
Author(s) -
Majima Masataka,
Toda Masaya,
Suzuki Tatsunori,
Hosono Kanako
Publication year - 2008
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.22.2_supplement.597
Subject(s) - calcitonin gene related peptide , angiogenesis , endocrinology , calcitonin , medicine , dorsal root ganglion , neuropeptide , neovascularization , in vivo , chemistry , receptor , biology , sensory system , neuroscience , microbiology and biotechnology
Calcitonin gene‐related peptide (CGRP) is a 37‐amino acid neuropeptide produced by tissue‐specific alternative splicing of calcitonin/CGRP gene. We examined whether or not endogenous CGRP facilitates neovascularization indispensable to tumor growth. The unilateral sciatic nerves of mice were cut, and Lewis lung carcinoma (LLC) cells were implanted into subcutaneous tissues of both legs. Tumor growth was significantly reduced in the sites of sensory nerve denervation. A CGRP antagonist, CGRP8‐37 suppressed LLC growth, compared with vehicle. In CGRP knockout mice (CGRP−/−), the tumor growth and tumor‐associated angiogenesis of LLC cells were significantly reduced compared with wild type mice (WT). In LLC bearing WT, CGRP precursor mRNA levels in dorsal root ganglion were increased compared with non‐treated mice. This increase was abolished by sensory nerve denervations. Further, we found that ulcer healing was significantly delayed in CGRP−/− with reductions in angiogenesis and VEGF expression. In culture system using HUVEC, CGRP increased tube formation. These results suggested that CGRP release from sensory nerves stimulated during tumor development and ulcer healing facilitates angiogenesis, and that CGRP may become a novel target of treatment for angiogenesis‐related pathological conditions.