Neuronal system-dependent facilitation of tumor angiogenesis and tumor growth by calcitonin gene-related peptide

Masaya Toda, Tatsunori Suzuki, Kanako Hosono, Izumi Hayashi, Shinichiro Hashiba, Yuichiro Onuma, Hideki Amano, Yukiko Kurihara, Hiroki Kurihara, Hirotsugu Okamoto, Sumio Hoka, Masataka Majima

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Abstract

A neuropeptide, calcitonin gene-related peptide (CGRP), is widely distributed in neuronal systems and exhibits numerous biological activities. Using CGRP-knockout mice (CGRP-/-), we examined whether or not endogenous CGRP facilitates angiogenesis indispensable to tumor growth. CGRP increased tube formation by endothelial cells in vitro and enhanced sponge-induced angiogenesis in vivo. Tumor growth and tumor-associated angiogenesis in CGRP-/- implanted with Lewis lung carcinoma (LLC) cells were significantly reduced compared with those in wild-type (WT) mice. A CGRP antagonist, CGRP8-37 or denervation of sciatic nerves (L1-5) suppressed LLC growth in the sites of denervation compared with vehicle infusion or sham operation. CGRP precursor mRNA levels in the dorsal root ganglion in LLC-bearing WT were increased compared with those in non-LLC-bearing mice. This increase was abolished by denervation. The expression of VEGF in tumor stroma was down-regulated in CGRP-/-. These results indicate that endogenous CGRP facilitates tumor-associated angiogenesis and tumor growth and suggest that relevant CGRP may be derived from neuronal systems including primary sensory neurons and may become a therapeutic target for cancers.

Original languageEnglish
Pages (from-to)13550-13555
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number36
DOIs
Publication statusPublished - Sep 9 2008

All Science Journal Classification (ASJC) codes

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    Toda, M., Suzuki, T., Hosono, K., Hayashi, I., Hashiba, S., Onuma, Y., Amano, H., Kurihara, Y., Kurihara, H., Okamoto, H., Hoka, S., & Majima, M. (2008). Neuronal system-dependent facilitation of tumor angiogenesis and tumor growth by calcitonin gene-related peptide. Proceedings of the National Academy of Sciences of the United States of America, 105(36), 13550-13555. https://doi.org/10.1073/pnas.0800767105