title: Neuronal system-dependent facilitation of tumor angiogenesis and tumor growth by calcitonin gene-related peptide.
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 (L(1-5)) 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.
authors.affiliation: Departments of Pharmacology and Anesthesiology, Kitasato University School of Medicine, Kanagawa 228-8555, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Toda
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kanako
authors.initials: K
authors.lastname: Hosono
authors.forename: Izumi
authors.initials: I
authors.lastname: Hayashi
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Hashiba
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Onuma
authors.forename: Hideki
authors.initials: H
authors.lastname: Amano
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kurihara
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurihara
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Okamoto
authors.forename: Sumio
authors.initials: S
authors.lastname: Hoka
authors.forename: Masataka
authors.initials: M
authors.lastname: Majima