Stromal and Epithelial Expression of Tumor Markers Hyaluronic Acid and HYAL1 Hyaluronidase in Prostate Cancer

Vinata B Lokeshwar, Diego Rubinowicz, Grethchen L. Schroeder, Eva Forgacs, John D. Minna, Norman L. Block, Mehrdad Nadji, Balakrishna L Lokeshwar

Research output: Contribution to journalArticle

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Abstract

Hyaluronic acid (HA), a glycosaminoglycan, regulates cell adhesion and migration. Hyaluronidase (HAase), an endoglycosidase, degrades HA into small angiogenic fragments. Using an enzyme-linked immunosorbent assay-like assay, we found increased HA levels (3-8-fold) in prostate cancer (CaP) tissues when compared with normal (NAP) and benign (BPH) tissues. The majority (∼75-80%) of HA in prostate tissues was found to exist in the free form. Primary CaP fibroblast and epithelial cells secreted 3-8-fold more HA than respective NAP and BPH cultures. Only CaP epithelial cells and established CaP lines secreted HAase and the secretion increased with tumor grade and metastasis. The pH activity profile and optimum (4.2; range 4.0-4.3) of CaP HAase was identical to the HYAL1-type HAase present in human serum and urine. Full-length HYAL1 transcript and splice variants were detected in CaP cells by reverse transcriptase-polymerase chain reaction, cloning, and sequencing. Immunoblotting confirmed secretion of a ∼60-kDa HYAL1-related protein by CaP cells. Immunohistochemistry showed minimal HA and HYAL1 staining in NAP and BPH tissues. However, a stromal and epithelial pattern of HA and HYAL1 expression was observed in CaP tissues. While high HA staining was observed in tumor-associated stroma, HYAL1 staining in tumor cells increased with tumor grade and metastasis. The gel-filtration column profiles of HA species in NAP, BPH, and CaP tissues were different. While the higher molecular mass and intermediate size HA was found in all tissues, the HA fragments were found only in CaP tissues. In particular, the high-grade CaP tissues, which showed both elevated HA and HYAL1 levels, contained angiogenic HA fragments. The stromal-epithelial HA and HYAL1 expression may promote angiogenesis in CaP and may serve as prognostic markers for CaP.

Original languageEnglish (US)
Pages (from-to)11922-11932
Number of pages11
JournalJournal of Biological Chemistry
Volume276
Issue number15
DOIs
StatePublished - Apr 13 2001

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Hyaluronoglucosaminidase
Hyaluronic Acid
Tumor Biomarkers
Prostatic Neoplasms
Tissue
Tumors
Staining and Labeling
Assays
Neoplasms
Epithelial Cells
Neoplasm Metastasis
Immunosorbents
Cloning
Glycoside Hydrolases
Polymerase chain reaction
RNA-Directed DNA Polymerase
Cell adhesion
Molecular mass
Fibroblasts
Glycosaminoglycans

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Stromal and Epithelial Expression of Tumor Markers Hyaluronic Acid and HYAL1 Hyaluronidase in Prostate Cancer. / Lokeshwar, Vinata B; Rubinowicz, Diego; Schroeder, Grethchen L.; Forgacs, Eva; Minna, John D.; Block, Norman L.; Nadji, Mehrdad; Lokeshwar, Balakrishna L.

In: Journal of Biological Chemistry, Vol. 276, No. 15, 13.04.2001, p. 11922-11932.

Research output: Contribution to journalArticle

Lokeshwar, Vinata B ; Rubinowicz, Diego ; Schroeder, Grethchen L. ; Forgacs, Eva ; Minna, John D. ; Block, Norman L. ; Nadji, Mehrdad ; Lokeshwar, Balakrishna L. / Stromal and Epithelial Expression of Tumor Markers Hyaluronic Acid and HYAL1 Hyaluronidase in Prostate Cancer. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 15. pp. 11922-11932.
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AU - Forgacs, Eva

AU - Minna, John D.

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AU - Nadji, Mehrdad

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