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An Antiproliferative Factor from Interstitial Cystitis Patients Is a Frizzled 8 Protein-Related Sialoglycopeptide
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An Antiproliferative Factor from Interstitial Cystitis Patients Is a Frizzled 8 Protein-Related Sialoglycopeptide
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Journal Article
An Antiproliferative Factor from Interstitial Cystitis Patients Is a Frizzled 8 Protein-Related Sialoglycopeptide
2004
Overview
Approximately 1 million people in the United States suffer from interstitial cystitis, a chronic painful urinary bladder disorder characterized by thinning or ulceration of the bladder epithelial lining; its etiology is unknown. We have identified a glycosylated frizzledrelated peptide inhibitor of cell proliferation that is secreted specifically by bladder epithelial cells from patients with this disorder. This antiproliferative factor (APF) profoundly inhibits bladder cell proliferation by means of regulation of cell adhesion protein and growth factor production. The structure of APF was deduced by using ion trap mass spectrometry (MS), enzymatic digestion, lectin affinity chromatography, and total synthesis, and confirmed by coelution of native and synthetic APF derivatives on microcapillary reversed-phase liquid chromatography (μRPLC)/MS. APF was determined to be an acidic, heat-stable sialoglycopeptide whose peptide chain has 100% homology to the putative sixth transmembrane domain of frizzled 8. Both synthetic and native APF had identical biological activity in normal bladder epithelial cells and T24 bladder cancer cells. Northern blot analysis indicated binding of a probe containing the sequence for the frizzled 8 segment with mRNA extracted from cells of patients with interstitial cystitis but not controls. APF is therefore a frizzled-related peptide growth inhibitor shown to contain exclusively a transmembrane segment of a frizzled protein and is a potential biomarker for interstitial cystitis.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ Antineoplastic Agents - analysis
/ Antineoplastic Agents - chemistry
/ Bladder
/ Cell Adhesion Molecules - analysis
/ Cell Adhesion Molecules - biosynthesis
/ Cell Division - drug effects
/ Chromatography, High Pressure Liquid
/ Cystitis, Interstitial - etiology
/ Cystitis, Interstitial - pathology
/ Epithelial Cells - pathology
/ Growth Substances - analysis
/ Growth Substances - biosynthesis
/ Humans
/ Intercellular Signaling Peptides and Proteins
/ Lectins
/ Peptide Fragments - analysis
/ Peptide Fragments - chemistry
/ Peptide Fragments - pharmacology
/ Proteins
/ RNA, Messenger - isolation & purification
/ Sialoglycoproteins - analysis
/ Sialoglycoproteins - chemistry
