Vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptor subtypes in human tumors and their tissues of origin.

Jun 13, 2000Cancer research

Types of VIP and PACAP Receptors in Human Tumors and Their Original Tissues

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Abstract

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) receptors are present in 100% of breast, prostate, and urinary bladder carcinomas.

VIP/PACAP receptor subtypes VPAC1, VPAC2, and PAC1 were identified in various human tumors using receptor autoradiography.
The majority of common tumors express VPAC1 receptors, with receptor incidence rates of 100% in breast and prostate cancers.
Other tumors, such as pancreatic and colon carcinomas, also show significant VPAC1 expression, with incidences of 65% and 96%, respectively.
Different tumor types exhibit varying receptor expression profiles, with leiomyomas primarily expressing VPAC2 and certain carcinomas preferring PAC1 receptors.
The distribution of VIP/PACAP receptors in normal tissues suggests a significant role in human physiology, while their overexpression in tumors could lead to potential clinical applications.

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The evaluation of peptide receptors in man is needed not only to discover the physiological target tissues of a given peptide but also to identify diseases with a sufficient receptor overexpression for diagnostic or therapeutic interventions. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) receptors have been evaluated in human tumors and in their tissues of origin using in vitro receptor autoradiography with 125I-VIP or 125I-acetyl-PACAP-27 in tissue sections. The VIP/PACAP receptor subtypes VPAC1, VPAC2, and PAC1 were evaluated in these tissues by determining the rank order of potencies of VIP and PACAP as well as VPAC1- and VPAC2-selective analogues. The VIP/PACAP receptors expressed in the great majority of the most frequently occurring human tumors, including breast (100% receptor incidence), prostate (100%), pancreas (65%), lung (58%), colon (96%), stomach (54%), liver (49%), and urinary bladder (100%) carcinomas as well as lymphomas (58%) and meningiomas (100%), are predominantly of the VPAC1 type. Their cells or tissues of origin, i.e., hepatocytes, breast lobules and ducts, urothelium, prostate glands, pancreatic ducts, lung acini, gastrointestinal mucosa, and lymphocytes, also predominantly express VPAC1. Leiomyomas predominantly express VPAC2 receptors, whereas paragangliomas, pheochromocytomas, and endometrial carcinomas preferentially express PAC1 receptors. Conversely, VPAC2 receptors are found mainly in smooth muscle (i.e., stomach), in vessels, and in stroma (e.g., of the prostate), whereas PAC1 receptors are present in the adrenal medulla and in some uterine glands. Whereas the very wide distribution of VIP/PACAP receptors in the normal human body is indicative of a key role of these peptides in human physiology, the high VIP/PACAP receptor expression in tumors may represent the molecular basis for clinical applications of VIP/PACAP such as in vivo scintigraphy and radiotherapy of tumors as well as VIP/PACAP analogue treatment for tumor growth inhibition.

Vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptor subtypes in human tumors and their tissues of origin.

Abstract

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