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 Miknyoczki, S. J. Articles by Buchkovich, K. Search for Related Content PubMed PubMed Citation Articles by Miknyoczki, S. J. Articles by Buchkovich, K.

The Neurotrophin-Trk Receptor Axes Are Critical for the Growth and Progression of Human Prostatic Carcinoma and Pancreatic Ductal Adenocarcinoma Xenografts in Nude Mice

Cephalon, Inc., West Chester, Pennsylvania 19380

Purpose: Aberrant expression of trk receptor kinases and enhanced expression of various neurotrophins (NTs) have been implicated in the development and progression of human prostatic carcinoma and pancreatic ductal adenocarcinoma. We examined the antitumor efficacy of administration of NT neutralizing antibodies on the growth of established human prostatic carcinoma and pancreatic ductal adenocarcinoma xenografts in nude mice.

Experimental Design: In initial studies, tumor-bearing nude mice were treated with a mixture of NT antibodies [100 µg each of anti-nerve growth factor (NGF), anti-brainderived neurotrophic factor, anti-NT-3, and anti-NT-4/5] or normal rabbit IgG (400 µg) intratumorally and peritumorally three times/week over a 15-day dosing period. In subsequent studies, tumor-bearing nude mice were treated with individual NT antibodies (100 µg), affinity-purified anti-NGF (0.1, 1.0, or 10.0 µg), or normal rabbit IgG (100 µg) using the same dosing schedule.

Results: Treatment with the antibody mixture inhibited significantly the growth of TSU-Pr1 and AsPC-1 xenografts as compared with IgG-treated controls (maximal inhibition of 53 and 53%, respectively), whereas this treatment caused significant regression in PC-3 xenografts. Treatment of TSU-Pr1 xenografts with either anti-NGF or anti-NT-3 resulted in maximal tumor growth inhibition of 67 and 64%, respectively, whereas anti-brain-derived neurotrophic factor and anti-NT-4/5 did not inhibit tumor growth in this tumor model. Administration of various concentrations (0.1, 1.0, or 10.0 µg) of affinity-purified anti-NGF resulted in maximal TSU-Pr1 tumor growth inhibition of 49, 62, and 66%, respectively.

Conclusions: These data add further support for the therapeutic potential of disrupting trk-signaling events in select types of nonneuronal human cancers, specifically prostatic and pancreatic carcinomas.

This article has been cited by other articles:

				E. Adriaenssens, E. Vanhecke, P. Saule, A. Mougel, A. Page, R. Romon, V. Nurcombe, X. Le Bourhis, and H. Hondermarck Nerve Growth Factor Is a Potential Therapeutic Target in Breast Cancer Cancer Res., January 15, 2008; 68(2): 346 - 351. [Abstract] [Full Text] [PDF]

				P. Carpinelli, R. Ceruti, M. L. Giorgini, P. Cappella, L. Gianellini, V. Croci, A. Degrassi, G. Texido, M. Rocchetti, P. Vianello, et al. PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer Mol. Cancer Ther., December 1, 2007; 6(12): 3158 - 3168. [Abstract] [Full Text] [PDF]

				M. Tometten, S. Blois, A. Kuhlmei, A. Stretz, B. F. Klapp, and P. C. Arck Nerve Growth Factor Translates Stress Response and Subsequent Murine Abortion via Adhesion Molecule-Dependent Pathways Biol Reprod, April 1, 2006; 74(4): 674 - 683. [Abstract] [Full Text] [PDF]

				R. N. Pearse, S. L. Swendeman, Y. Li, D. Rafii, and B. L. Hempstead A neurotrophin axis in myeloma: TrkB and BDNF promote tumor-cell survival Blood, June 1, 2005; 105(11): 4429 - 4436. [Abstract] [Full Text] [PDF]

				K. Ketterer, S. Rao, H. Friess, J. Weiss, M. W. Buchler, and M. Korc Reverse Transcription-PCR Analysis of Laser-Captured Cells Points to Potential Paracrine and Autocrine Actions of Neurotrophins in Pancreatic Cancer Clin. Cancer Res., November 1, 2003; 9(14): 5127 - 5136. [Abstract] [Full Text] [PDF]

				B. Davidson, R. Reich, P. Lazarovici, J. M. Nesland, M. Skrede, B. Risberg, C. G. Trope, and V. A. Florenes Expression and Activation of the Nerve Growth Factor Receptor TrkA in Serous Ovarian Carcinoma Clin. Cancer Res., June 1, 2003; 9(6): 2248 - 2259. [Abstract] [Full Text] [PDF]