Cytokeratin 5–Positive Cells Represent a Therapy Resistant subpopulation in Epithelial Ovarian Cancer (2)

Science News

CK5 marks cisplatin-resistant ovarian cancer Source: University of Colorado Anschutz Medical Campus

Summary:

Protein cytokeratin 5 (CK5), known to be a marker of poor prognosis in breast cancer, also marks ovarian cancers likely to be resistant to the common chemotherapy cisplatin, new research confirms.

   "It's interesting that CK5-positive cells pop up as bad actors across many cancer types. Now the challenge is to find a functional role for the protein in cancer. What's functionally different about those cells?" Sartorius says.

abstract
 

Objective: Cytokeratin 5 (CK5) is an epithelial cell marker implicated in stem and progenitor cell activity in glandular reproductive tissues and endocrine and chemotherapy resistance in estrogen receptor (ER)⁺ breast cancer. The goal of this study was to determine the prevalence of CK5 expression in ovarian cancer and the response of CK5⁺ cell populations to cisplatin therapy.

Materials and Methods: Cytokeratin 5 expression was evaluated in 2 ovarian tissue microarrays, representing 137 neoplasms, and 6 ovarian cancer cell lines. Cell lines were treated with IC₅₀ (half-maximal inhibitory concentration) cisplatin, and the prevalence of CK5⁺ cells pretreatment and posttreatment was determined. Proliferation of CK5⁺ versus CK5⁻ cell populations was determined using 5-bromo-2′-deoxyuridine incorporation. Chemotherapy-induced apoptosis in CK5⁺ versus CK5⁻ cells was measured using immunohistochemical staining for cleaved caspase-3.

Results: Cytokeratin 5 was expressed in 39.3% (42 of 107) of epithelial ovarian cancers with a range of 1% to 80% positive cells. Serous and endometrioid histologic subtypes had the highest percentage of CK5⁺ specimens. Cytokeratin 5 expression correlated with ER positivity (38 of 42 CK5⁺ tumors were also ER⁺). Cytokeratin 5 was expressed in 5 of 6 overall and 4 of 4 ER⁺ epithelial ovarian cancer cell lines ranging from 2.4% to 52.7% positive cells. Cytokeratin 5⁺ compared with CK5⁻ cells were slower proliferating. The prevalence of CK5⁺ cells increased after 48-hour cisplatin treatment in 4 of 5 cell lines tested. Cytokeratin 5⁺ ovarian cancer cells compared with CK5⁻ ovarian cancer cells were more resistant to cisplatin-induced apoptosis.

Conclusions: Cytokeratin 5 is expressed in a significant proportion of epithelial ovarian cancers and represents a slower proliferating chemoresistant subpopulation that may warrant cotargeting in combination therapy.