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Effect of gastrin‐releasing peptide on the pancreatic tumor cell line (capan)
Author(s) -
Avis Ingalill,
Cuttitta Frank,
Treston Anthony M.,
Mulshine James L.,
Jett Marti,
Kasprzyk Philip G.,
Maneckjee Rhoda
Publication year - 1993
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940080403
Subject(s) - gastrin releasing peptide , bombesin , autocrine signalling , biology , receptor , paracrine signalling , cell culture , gastrin , peptide , microbiology and biotechnology , growth factor , medicine , endocrinology , biochemistry , neuropeptide , genetics , secretion
Gastrin‐releasing peptide (GRP) has previously been shown to be an autocrine growth factor for small cell lung cancer, and our objective in the study presented here was to determine whether GRP has a similar role in pancreatic cancer. Using 125 I‐GRP, we demonstrated binding to specific, saturable, high‐affinity sites ( K d =1 nM; B max =245 fmol/mg protein) in membrane preparations from the pancreatic tumor cell line Capan. The receptors were found to be biologically active. In whole cells, a GRP analogue bound to these receptors and stimulated rapid transfer of tritium from the tritiated lipid inositol pool to inositol triphosphates. Exogenous GRP addition stimulated incorporation of [ 3 H]thymidine into DNA 20–60%. This stimulatory effect was blocked by the addition of a monoclonal antibody that complexed specifically with the receptor‐binding portion of the peptide. In addition, the monoclonal antibody inhibited the growth of Capan cells in an in vitro growth assay without exogenous peptide. Bombesin receptor—specific antagonists also inhibited growth in a similar fashion. These data suggest that paracrine production of GRP may be important in pancreatic tumor growth, or that low‐levels of a GRP‐like peptide may play an autocrine role in this tumor. © 1993 Wiley‐Liss, Inc.