Shedding of Distinct Cryptic Collagen Epitope (HU177) in Sera of Melanoma Patients

Purpose: Extracellular matrix remodeling during tumor growth plays an important role in angiogenesis. Our preclinical data suggest that a newly identified cryptic epitope (HU177) within collagen type IV regulates endothelial and melanoma cell adhesion in vitro and angiogenesis in vivo . In this stud...

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Published in:	Clinical cancer research Vol. 14; no. 19; pp. 6253 - 6258
Main Authors:	NG, Bruce, ZAKRZEWSKI, Jan, MONTGOMERY, Anthony, LIEBES, Leonard, BROOKS, Peter C, OSMANL, Iman, WARYCHA, Melanie, CHRISTOS, Paul J, BAJORIN, Dean F, SHAPIRO, Richard L, BERMAN, Russell S, PAVLICK, Anna C, POLSKY, David, MAZUMDAR, Madhu
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA American Association for Cancer Research 01-10-2008
Subjects:	Adult Aged Aged, 80 and over Antineoplastic agents Biological and medical sciences Cell Adhesion Cohort Studies Collagen - chemistry Collagen Type IV - biosynthesis Collagen Type IV - chemistry Collagen Type IV - metabolism cryptic epitope Dermatology Epitopes - chemistry Extracellular Matrix - metabolism Female Gene Expression Regulation, Neoplastic Humans Male Medical sciences melanoma Melanoma - blood Melanoma - metabolism Middle Aged Neoplasms - metabolism Neovascularization, Pathologic Pharmacology. Drug treatments Tumors of the skin and soft tissue. Premalignant lesions type IV collagen Human Antigenic determinant Collagen Glycoprotein Malignant melanoma Patient Serum Malignant tumor Cancer Cryptic antigen
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Summary:	Purpose: Extracellular matrix remodeling during tumor growth plays an important role in angiogenesis. Our preclinical data suggest that a newly identified cryptic epitope (HU177) within collagen type IV regulates endothelial and melanoma cell adhesion in vitro and angiogenesis in vivo . In this study, we investigated the clinical relevance of HUI77 shedding in melanoma patient sera. Experimental Design: Serum samples from 291 melanoma patients prospectively enrolled at the New York University Medical Center and 106 control subjects were analyzed for HU177 epitope concentration by a newly developed sandwich ELISA assay. HU177 serum levels were then correlated with clinical and pathologic parameters. Results: Mean HU177 epitope concentration was 5.8 ng/mL (range, 0-139.8 ng/mL). A significant correlation was observed between HU177 concentration and nodular melanoma histologic subtype [nodular, 10.3 ± 1.6 ng/mL (mean ± SE); superficial spreading melanoma, 4.5 ± 1.1 ng/mL; all others, 6.1 ± 2.1 ng/mL; P = 0.01 by ANOVA test]. Increased HU177 shedding also correlated with tumor thickness (≤1.00 mm, 3.8 ± 1.1 ng/mL; 1.01-3.99 mm, 8.7 ± 1.3 ng/mL; ≥4.00 mm, 10.3 ± 2.4 ng/mL; P = 0.003 by ANOVA). After multivariate analysis controlling for thickness, the correlation between higher HU177 concentration and nodular subtype remained significant ( P = 0.03). The mean HU177 epitope concentration in control subjects was 2.4 ng/mL. Conclusions: We report that primary melanoma can induce detectable changes in systemic levels of cryptic epitope shedding. Our data also support that nodular melanoma might be biologically distinct compared with superficial spreading type melanoma. As targeted interventions against cryptic collagen epitopes are currently undergoing phase I clinical trial testing, these findings indicate that patients with nodular melanoma may be more susceptible to such targeted therapies.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Current address: Peter C. Brooks. Maine Medical Center Research Institute, 81 Research Drive. Scarborough, ME 04074 contributed equally
ISSN:	1078-0432 1557-3265
DOI:	10.1158/1078-0432.CCR-07-4992