title: Expression of hedgehog pathway components in prostate carcinoma microenvironment: shifting the balance towards autocrine signalling.
abstract: OBJECTIVE
  The hedgehog (Hh) signalling pathway has been implicated in the pathogenesis and aggressiveness of prostate cancer through epithelial-mesenchymal interactions. The aim of this study was to elucidate the cell-type partitioned expression of the Hh pathway biomarkers in the non-neoplastic and tumour microenvironments and to correlate it with the grade and stage of prostate cancer.
  
  
  RESULTS
  Expression of the Hh pathway components (Shh, Smo, Ptch, Gli1) in the microenvironment of non-neoplastic peripheral zone (n = 119), hormone-naive primary prostate carcinoma (n = 141) and castrate-resistant bone marrow metastases (n = 53) was analysed using immunohistochemistry in tissue microarrays and bone marrow sections. Results showed that epithelial Shh, Smo and Ptch expression was up-regulated, whereas stromal Smo, Ptch, and Gli1 expression was down-regulated in prostate carcinomas compared to non-neoplastic peripheral zone tissue. Ptch expression was modulated further in high-grade and high-stage primary tumours and in bone marrow metastases. Hh signalling correlated with ki67 and vascular endothelial growth factor (VEGF) but not with CD31 expression.
  
  
  CONCLUSIONS
  Our results highlight the importance of Hh-mediated epithelial-mesenchymal interactions in the non-neoplastic prostate and imply that shifting the balance from paracrine towards autocrine signalling is important in the pathogenesis and progression of prostate carcinoma.
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77230, USA.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Tzelepi
authors.forename: Maria
authors.initials: M
authors.lastname: Karlou
authors.forename: Sijin
authors.initials: S
authors.lastname: Wen
authors.forename: Anh
authors.initials: A
authors.lastname: Hoang
authors.forename: Christopher
authors.initials: C
authors.lastname: Logothetis
authors.forename: Patricia
authors.initials: P
authors.lastname: Troncoso
authors.forename: Eleni
authors.initials: E
authors.lastname: Efstathiou
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary; D000328:Adult; D000368:Aged; D019898:Autocrine Communication / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D019046:Bone Marrow Neoplasms / Q000378:metabolism / Q000556:secondary; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D053823:Hedgehog Proteins; C509239:SHH protein, human