title: Epithelial and stromal cathepsin K and CXCL14 expression in breast tumor progression.
abstract: OBJECTIVE
  To evaluate the expression of cathepsin K (CTSK) and CXCL14 in stromal and epithelial cells in human breast tumor progression.
  
  
  METHODS
  We did immunohistochemical analyses of CTSK and CXCL14 expression in normal breast tissue, biopsy sites, benign lesions, ductal carcinoma in situ, and invasive breast tumors of different stages. Expression patterns were related to histopathologic characteristics of the tumors and clinical outcome. The effect of CTSK+ breast stromal fibroblasts on CTSK- breast cancer cells was assessed in coculture.
  
  
  RESULTS
  Epithelial expression of CTSK was rarely detected in any of the tissue samples analyzed, whereas CXCL14-positive epithelial cells were found in all tissue types. The expression of CXCL14 was not associated with any tumor or patient characteristics analyzed. Stromal CTSK expression was significantly higher in invasive compared with in situ carcinomas, and in one of the two data sets analyzed, it correlated with higher tumor stage. Among all samples examined, the highest stromal CTSK levels were detected in biopsy sites. Neither epithelial nor stromal expression of CTSK was significantly associated with recurrence-free or overall survival. Coculture of CTSK+ fibroblasts enhanced the invasion of CTSK- breast tumor epithelial cells and this was blocked by CTSK inhibitors.
  
  
  CONCLUSIONS
  CTSK may function as a paracrine factor in breast tumorigenesis. CTSK+ fibroblasts may play a role in tumor progression by promoting the invasiveness of tumor epithelial cells. The possibility that CTSK inhibitors may have a clinical role in decreasing the risk of tumor progression merits further investigation.
authors.affiliation: Department of Pathology, University of Michigan Cancer Center, Ann Arbor, Michigan, USA.
authors.forename: Celina G
authors.initials: CG
authors.lastname: Kleer
authors.forename: Noga
authors.initials: N
authors.lastname: Bloushtain-Qimron
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Chen
authors.forename: Daniel
authors.initials: D
authors.lastname: Carrasco
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.forename: Stine-Kathrein
authors.initials: SK
authors.lastname: Kraeft
authors.forename: Laura C
authors.initials: LC
authors.lastname: Collins
authors.forename: Michael S
authors.initials: MS
authors.lastname: Sabel
authors.forename: Pedram
authors.initials: P
authors.lastname: Argani
authors.forename: Rebecca
authors.initials: R
authors.lastname: Gelman
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Schnitt
authors.forename: Ian E
authors.initials: IE
authors.lastname: Krop
authors.forename: Kornelia
authors.initials: K
authors.lastname: Polyak