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Author Notes:

Correspondence to: Mary C. Farach-Carson, Email: farachca@rice.edu

The authors declare that they have no conflicts of interest.

Subjects:

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • Cell Biology
  • perlecan
  • matrilysin
  • prostate cancer
  • metastasis
  • invasion
  • HEPARAN-SULFATE PROTEOGLYCAN
  • MATRIX-METALLOPROTEINASE 7
  • GROWTH-FACTOR
  • TUMOR MICROENVIRONMENT
  • BASEMENT-MEMBRANE
  • BONE METASTASIS
  • CELL-ADHESION
  • IN-SITU
  • CANCER
  • EXPRESSION

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

Tools:

Journal Title:

Oncotarget

Volume:

Volume 7, Number 9

Publisher:

, Pages 10433-10447

Type of Work:

Article | Final Publisher PDF

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 proteasesubstrate 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.

Copyright information:

© 2016 Grindel et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/).

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