Oncotarget

Research Papers:

This article has been corrected. Correction in: Oncotarget. 2016; 7(37):60775.

Perlecan/HSPG2 and matrilysin/MMP-7 as indices of tissue invasion: tissue localization and circulating perlecan fragments in a cohort of 288 radical prostatectomy patients

Brian Grindel, Quanlin Li, Rebecca Arnold, John Petros, Majd Zayzafoon, Mark Muldoon, James Stave, Leland W. K. Chung and Mary C. Farach-Carson _

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Oncotarget. 2016; 7:10433-10447. https://doi.org/10.18632/oncotarget.7197

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Abstract

Brian Grindel1, Quanlin Li2, Rebecca Arnold3, John Petros3,4, Majd Zayzafoon5, Mark Muldoon6,9, James Stave6,10, Leland W. K. Chung7, Mary C. Farach-Carson1,8

1Department of BioSciences, Rice University, Houston, TX 77005, USA

2Biostatistics and Bioinformatics Research Center, Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA

3Emory University Departments of Urology, Pathology and Laboratory Medicine and Hematology and Medical Oncology, Atlanta, GA 30322, USA

4The Atlanta Veteran Affairs Medical Center, Decatur, GA 30033, USA

5Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35233, USA

6Strategic Diagnostics Inc., Newark, DE 19702, USA

7Uro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA

8Department of Bioengineering, Rice University, Houston, TX 77005, USA

9Romer Labs Technology, Inc., Newark, DE 19713, USA

10CD Diagnostics, Claymont, DE 19703, USA

Correspondence to:

Mary C. Farach-Carson, e-mail: farachca@rice.edu

Keywords: perlecan, matrilysin, prostate cancer, metastasis, invasion

Received: July 09, 2015     Accepted: January 01, 2016     Published: February 04, 2016

ABSTRACT

Prostate cancer (PCa) cells use matrix metalloproteinases (MMPs) to degrade tissue during invasion. Perlecan/HSPG2 is degraded at basement membranes, in reactive stroma and in bone marrow during metastasis. We previously showed MMP-7 efficiently degrades perlecan. We now analyzed PCa tissue and serum from 288 prostatectomy patients of various Gleason grades to decipher the relationship between perlecan and MMP-7 in invasive PCa. In 157 prostatectomy specimens examined by tissue microarray, perlecan levels were 18% higher than their normal counterparts. In Gleason grade 4 tissues, MMP-7 and perlecan immunostaining levels were highly correlated with each other (average correlation coefficient of 0.52) in PCa tissue, regardless of grade. Serial sections showed intense, but non-overlapping, immunostaining for MMP-7 and perlecan at adjacent borders, reflecting the protease-substrate relationship. Using a capture assay, analysis of 288 PCa sera collected at prostatectomy showed elevated levels of perlecan fragments, with most derived from domain IV. Perlecan fragments in PCa sera were associated with overall MMP-7 staining levels in PCa tissues. Domain IV perlecan fragments were present in stage IV, but absent in normal, sera, suggesting perlecan degradation during metastasis. Together, perlecan fragments in sera and MMP-7 in tissues of PCa patients are measures of invasive PCa.


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