title: 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.
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.
authors: Department of BioSciences, Rice University, Houston, TX 77005, USA.
authors: Brian
authors: B
authors: Grindel
authors: Biostatistics and Bioinformatics Research Center, Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA.
authors: Quanlin
authors: Q
authors: Li
authors: Emory University Departments of Urology, Pathology and Laboratory Medicine and Hematology and Medical Oncology, Atlanta, GA 30322, USA.
authors: Rebecca
authors: R
authors: Arnold
authors: Emory University Departments of Urology, Pathology and Laboratory Medicine and Hematology and Medical Oncology, Atlanta, GA 30322, USA.|The Atlanta Veteran Affairs Medical Center, Decatur, GA 30033, USA.
authors: John
authors: J
authors: Petros
authors: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
authors: Majd
authors: M
authors: Zayzafoon
authors: Strategic Diagnostics Inc., Newark, DE 19702, USA.|Romer Labs Technology, Inc., Newark, DE 19713, USA.
authors: Mark
authors: M
authors: Muldoon
authors: Strategic Diagnostics Inc., Newark, DE 19702, USA.|CD Diagnostics, Claymont, DE 19703, USA.
authors: James
authors: J
authors: Stave
authors: Uro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors: Leland W K
authors: LW
authors: Chung
authors: Department of BioSciences, Rice University, Houston, TX 77005, USA.|Department of Bioengineering, Rice University, Houston, TX 77005, USA.
authors: Mary C
authors: MC
authors: Farach-Carson
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood* / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000097:blood* / Q000378:metabolism; D006801:Humans; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness / Q000473:pathology; D011467:Prostate / Q000473:pathology*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology* / Q000601:surgery; D001613:beta 2-Microglobulin / Q000097:blood / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D019812:Heparan Sulfate Proteoglycans; D001613:beta 2-Microglobulin; C071927:perlecan; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7
keywords: invasion; matrilysin; metastasis; perlecan; prostate cancer