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

Research output: Contribution to journalArticle

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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

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Calcitonin Gene-Related Peptide
Growth
Lewis Lung Carcinoma
Neoplasms
Denervation
Spinal Ganglia
Porifera
Sensory Receptor Cells
Sciatic Nerve
Neuropeptides
Knockout Mice
Vascular Endothelial Growth Factor A
Endothelial Cells
Carcinoma
Lung
Messenger RNA

All Science Journal Classification (ASJC) codes

  • General

Cite this

Neuronal system-dependent facilitation of tumor angiogenesis and tumor growth by calcitonin gene-related peptide. / Toda, Masaya; Suzuki, Tatsunori; Hosono, Kanako; Hayashi, Izumi; Hashiba, Shinichiro; Onuma, Yuichiro; Amano, Hideki; Kurihara, Yukiko; Kurihara, Hiroki; Okamoto, Hirotsugu; Hoka, Sumio; Majima, Masataka.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 36, 09.09.2008, p. 13550-13555.

Research output: Contribution to journalArticle

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, vol. 105, no. 36, pp. 13550-13555. https://doi.org/10.1073/pnas.0800767105
Toda, Masaya ; Suzuki, Tatsunori ; Hosono, Kanako ; Hayashi, Izumi ; Hashiba, Shinichiro ; Onuma, Yuichiro ; Amano, Hideki ; Kurihara, Yukiko ; Kurihara, Hiroki ; Okamoto, Hirotsugu ; Hoka, Sumio ; Majima, Masataka. / Neuronal system-dependent facilitation of tumor angiogenesis and tumor growth by calcitonin gene-related peptide. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 36. pp. 13550-13555.
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