TY - JOUR
T1 - Epithelial and stromal cathepsin K and CXCL14 expression in breast tumor progression
AU - Kleer, Celina G.
AU - Bloushtain-Qimron, Noga
AU - Chen, Yu Hui
AU - Carrasco, Daniel
AU - Hu, Min
AU - Yao, Jun
AU - Kraeft, Stine Kathrein
AU - Collins, Laura C.
AU - Sabel, Michael S.
AU - Argani, Pedram
AU - Gelman, Rebecca
AU - Schnitt, Stuart J.
AU - Krop, Ian E.
AU - Polyak, Kornelia
PY - 2008/9/1
Y1 - 2008/9/1
N2 - Purpose: To evaluate the expression of cathepsin K (CTSK) and CXCL14in stromal and epithelial cells in human breast tumor progression. Experimental Design: We did immunohistochemical analyses of CTSK and CXCL14expression 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.
AB - Purpose: To evaluate the expression of cathepsin K (CTSK) and CXCL14in stromal and epithelial cells in human breast tumor progression. Experimental Design: We did immunohistochemical analyses of CTSK and CXCL14expression 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.
UR - http://www.scopus.com/inward/record.url?scp=53049084066&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=53049084066&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-08-0732
DO - 10.1158/1078-0432.CCR-08-0732
M3 - Article
C2 - 18765527
AN - SCOPUS:53049084066
SN - 1078-0432
VL - 14
SP - 5357
EP - 5367
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 17
ER -