In:
Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 10, No. 24 ( 2004-12-15), p. 8235-8242
Abstract:
Human tumors frequently overexpress receptors for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP). However, none of the VIP/PACAP receptor proteins has been visualized individually in human tumors. Here, we developed and characterized a panel of antipeptide antibodies to the carboxyl-terminal regions of the VIP/PACAP receptor subtypes vasoactive intestinal peptide receptor (VPAC)1, VPAC2, and pituitary adenylate cyclase-activating peptide receptor (PAC)1. Specificity of the antisera was shown by the following: (1) detection of broad bands migrating at Mr 50,000 to 70,000 in Western blots of membranes from receptor-expressing tumors and receptor-transfected cells; (2) cell surface staining of VIP/PACAP receptor-transfected cells; (3) translocation of VIP/PACAP receptor immunostaining in transfected cells after agonist exposure; and (4) abolition of tissue immunostaining by preadsorbtion of the antibodies with their immunizing peptides. The distribution of VIP/PACAP receptors was investigated in 98 human tumors and their tissues of origin. VPAC1, VPAC2, and PAC1 receptors were clearly located at the plasma membrane of the tumor cells in a variety of human neoplasms. In the gastrointestinal tract, VPAC1 receptor immunoreactivity was abundant in the mucosa and myenteric neurons; VPAC2 receptor immunoreactivity was detected in neuroendocrine cells, blood vessels, and smooth muscle; and PAC1 receptor immunoreactivity was found in myenteric neurons. This is the first localization of all of the VIP/PACAP receptor subtypes in human formalin-fixed, paraffin-embedded tissues. VIP/PACAP receptor visualization with this simple and rapid immunohistochemical method will facilitate identification of tumors with a sufficient receptor overexpression for diagnostic or therapeutic intervention.
Type of Medium:
Online Resource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1078-0432.CCR-04-0939
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2004
detail.hit.zdb_id:
1225457-5
detail.hit.zdb_id:
2036787-9
