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The Neurotrophin-Trk Receptor Axes Are Critical for the Growth and Progression of Human Prostatic Carcinoma and Pancreatic Ductal Adenocarcinoma Xenografts in Nude Mice
Ist Teil von
Clinical cancer research, 2002-06, Vol.8 (6), p.1924-1931
Ort / Verlag
Philadelphia, PA: American Association for Cancer Research
Erscheinungsjahr
2002
Quelle
MEDLINE
Beschreibungen/Notizen
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.