This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chigurupati, S. Articles by Shah, G. Search for Related Content PubMed PubMed Citation Articles by Chigurupati, S. Articles by Shah, G.

Calcitonin Stimulates Multiple Stages of Angiogenesis by Directly Acting on Endothelial Cells

Department of Pharmacology, University of Louisiana School of Pharmacy, College of Health Sciences, Monroe, Louisiana

Requests for reprints: Girish V. Shah, Department of Pharmaceutical Sciences, School of Pharmacy, University of Louisiana, 700 University Avenue, Monroe, LA 71209. Phone: 318-342-1693; Fax: 318-342-1737; E-mail: shah{at}ulm.edu.

Although a strong correlation between neuroendocrine differentiation and angiogenesis of prostate cancer has been reported, no mechanistic link between the two events has been established. Because neuropeptide calcitonin is secreted by prostate tumors and endothelial cells are known to express calcitonin receptor–like receptor, we examined the potential action of calcitonin on endothelial cells. The presence of calcitonin receptor, calcitonin receptor–like receptor, and receptor activity–modifying proteins in human microvessel endothelial-1 cells was tested by reverse transcriptase-PCR (RT-PCR). The proangiogenic action of calcitonin was examined in several in vitro models of angiogenesis using HMEC-1 cells and also in vivo using dorsal skinfold assays. Calcitonin expression of PC-3M cells was modulated, and its effect on angiogenesis was examined in in vitro as well as in vivo models. The results of RT-PCR and radioligand receptor assays showed the presence of functional calcitonin receptor in HMEC-1 cells. Calcitonin stimulated all phases of angiogenesis through the calcitonin receptor, but its effect on tube morphogenesis by endothelial cells occurred at the concentration of the K_d of calcitonin receptor. Silencing of calcitonin receptor expression in HMEC-1 cells abolished calcitonin-induced tube formation. Vascular endothelial growth factor antibodies attenuated but did not abolish calcitonin-induced tube morphogenesis. PC-3M prostate cancer cells induced angiogenesis in in vivo and in vitro models. Overexpression of calcitonin in PC-3M cells increased their angiogenic activity, whereas the silencing of calcitonin expression abolished it. These results show that prostate tumor–derived calcitonin may play an important role in prostate tumor growth by regulating intratumoral vascularization.

This article has been cited by other articles:

				M. Joao Bugalho, D. Madureira, C. Espadinha, A. Paula Font, and L. G Sobrinho Serum vascular endothelial growth factor levels in patients with medullary thyroid carcinoma Eur. J. Endocrinol., August 1, 2008; 159(2): 167 - 169. [Abstract] [Full Text] [PDF]

				M. Nakamura, B. Han, T. Nishishita, Y. Bai, and K. Kakudo Calcitonin targets extracellular signal-regulated kinase signaling pathway in human cancers J. Mol. Endocrinol., December 1, 2007; 39(6): 375 - 384. [Abstract] [Full Text] [PDF]