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Different phenotypes in human prostate cancer: alpha6 or alpha3 integrin in cell-extracellular adhesion sites.

Abstract
The distribution of alpha6/alpha3 integrin in adhesion complexes at the basal membrane in human normal and cancer prostate glands was analyzed in 135 biopsies from 61 patients. The levels of the polarized alpha6/alpha3 integrin expression at the basal membrane of prostate tumor glands were determined by quantitative immunohistochemistry. The alpha6/alpha3 integrin expression was compared with Gleason sum score, pathological stage, and preoperative serum prostate-specific antigen (PSA). The associations were assessed by statistical methods. Eighty percent of the tumors expressed the alpha6 or alpha3 integrin and 20% was integrin-negative. Gleason sum score, but not serum PSA, was associated with the integrin expression. Low Gleason sum score correlated with increased integrin expression, high Gleason sum score with low and negative integrin expression. Three prostate tumor phenotypes were distinguished based on differential integrin expression. Type I coexpressed both alpha6 and alpha3 subunits, type II exclusively expressed alpha6 integrin, and type III expressed alpha3 integrin only. Fifteen cases were further examined for the codistribution of vinculin, paxillin, and CD 151 on frozen serial sections using confocal laser scanning microscopy. The alpha6/alpha3 integrins, CD151, paxillin, and vinculin were present within normal glands. In prostate carcinoma, alpha6 integrin was colocalized with CD 151, but not with vinculin or paxillin. In tumor phenotype I, the alpha6 subunit did not colocalize with the alpha subunit indicating the existence of two different adhesion complexes. Human prostate tumors display on their cell surface the alpha6beta1 and/or alpha3beta1 integrins. Three tumor phenotypes associated with two different adhesion complexes were identified, suggesting a reorganization of cell adhesion structures in prostate cancer.
AuthorsMonika Schmelz, Anne E Cress, Katherine M Scott, Friederike Bürger, Haiyan Cui, Karim Sallam, Kathy M McDaniel, Bruce L Dalkin, Raymond B Nagle
JournalNeoplasia (New York, N.Y.) (Neoplasia) 2002 May-Jun Vol. 4 Issue 3 Pg. 243-54 ISSN: 1522-8002 [Print] United States
PMID11988844 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antigens, CD
  • CD151 protein, human
  • Cytoskeletal Proteins
  • Integrin alpha3
  • Integrin alpha6
  • Integrins
  • PXN protein, human
  • Paxillin
  • Phosphoproteins
  • Tetraspanin 24
  • Vinculin
  • Prostate-Specific Antigen
Topics
  • Alleles
  • Antigens, CD (biosynthesis)
  • Binding Sites
  • Biopsy
  • Cell Adhesion
  • Cytoskeletal Proteins (metabolism)
  • Humans
  • Immunohistochemistry
  • Integrin alpha3
  • Integrin alpha6
  • Integrins (biosynthesis)
  • Male
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Mutation
  • Paxillin
  • Phenotype
  • Phosphoproteins (metabolism)
  • Prostate-Specific Antigen (biosynthesis)
  • Prostatic Neoplasms (metabolism)
  • Tetraspanin 24
  • Vinculin (metabolism)

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