title: Prostate cancer increases hyaluronan in surrounding nonmalignant stroma, and this response is associated with tumor growth and an unfavorable outcome.
abstract: Our objective was to investigate whether the presence of a tumor increases hyaluronan (HA) levels in surrounding prostate tissues and whether this extratumoral HA influences tumor growth and outcome. From a series of 287 men diagnosed with prostate cancer at transurethral resection and followed up with watchful waiting, tissue microarrays were constructed, stained, and scored for HA. A high HA staining score in the tumor stroma or in nonmalignant prostate tissue stroma were both associated positively with higher Gleason score and larger tumor volume, and was associated with a poor outcome. HA staining score was not an independent marker for outcome (multivariate Cox, with Gleason score, tumor volume, stage, and HA variables). In an orthotopic rat prostate cancer model, hyaluronic acid synthase-1 mRNA levels and HA staining were increased in normal prostate tissue surrounding prostate cancer. Orthotopic prostate cancer growth was increased by intraprostatic injection of HA. In conclusion, cancer in the prostate apparently stimulates HA synthesis both in tumor stroma and in the surrounding normal tissue. This promoted tumor growth and was associated with an unfavorable outcome.
authors.affiliation: Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden. andreas.josefsson@medbio.umu.se
authors.forename: Andreas
authors.initials: A
authors.lastname: Josefsson
authors.forename: Hani
authors.initials: H
authors.lastname: Adamo
authors.forename: Peter
authors.initials: P
authors.lastname: Hammarsten
authors.forename: Torvald
authors.initials: T
authors.lastname: Granfors
authors.forename: Pär
authors.initials: P
authors.lastname: Stattin
authors.forename: Lars
authors.initials: L
authors.lastname: Egevad
authors.forename: Anna Engström
authors.initials: AE
authors.lastname: Laurent
authors.forename: Pernilla
authors.initials: P
authors.lastname: Wikström
authors.forename: Anders
authors.initials: A
authors.lastname: Bergh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation; D014453:Glucuronosyltransferase / Q000378:metabolism; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D013194:Staining and Labeling; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome; D057832:Watchful Waiting
chemical_list: D014408:Biomarkers, Tumor; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C523794:HAS1 protein, human; D000076002:Hyaluronan Synthases