Epothilone B enhances surface EpCAM expression in ovarian cancer Hey cells

Shohreh Shahabi, Chia-Ping H. Yang, Gary L. Goldberg, Susan Band Horwitz

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Objectives: Epothilone B (EpoB), like Taxol, stabilizes microtubules resulting in an inhibition of microtubule dynamic instability. The drug is being evaluated in phase III clinical trials. An EpoB analog, Ixabepilone, was approved by the FDA for the treatment of taxane-resistant metastatic breast cancer. Epithelial cell adhesion antigen (EpCAM) expression is significantly higher in epithelial ovarian cancer cells compared to normal cells. The effects of EpoB and other microtubule-interacting agents on surface EpCAM expression were studied. Methods: Biochemical methods, immunofluorescence and flow cytometry were used to identify EpCAM expression on the surface of the ovarian cancer cell line, Hey, after exposure to EpoB. The relationship between EpoB-mediated surface EpCAM expression and EpoB-induced α-tubulin acetylation, a surrogate marker for stable microtubules, in Hey cells also was investigated. Results: Nanomolar concentrations of EpoB, Taxol, discodermolide or vinblastine caused a marked increase in surface EpCAM expression in Hey cells. Alpha-tubulin acetylation was increased following treatment with Taxol, EpoB and discodermolide, but not with vinblastine, indicating that drug-enhanced surface EpCAM expression does not correlate with tubulin acetylation or stabilization. Unexpectedly, EpoB did not have a significant effect on EpCAM mRNA expression, nor did it alter the level of total cellular EpCAM in Hey cells. Conclusions: The results indicate that disruption of the microtubule cytoskeleton is associated with the redistribution of cell surface antigens in ovarian cancer cells. The increase in cell surface EpCAM antigen density may facilitate the antibody targeting of EpCAM-positive ovarian cancer cells.

Original languageEnglish (US)
Pages (from-to)345-350
Number of pages6
JournalGynecologic Oncology
Volume119
Issue number2
DOIs
StatePublished - Nov 2010

Fingerprint

Ovarian Neoplasms
Microtubules
Tubulin
Acetylation
Vinblastine
Surface Antigens
Paclitaxel
Epithelial Cell Adhesion Molecule
epothilone B
Phase III Clinical Trials
Cytoskeleton
Cell Adhesion
Pharmaceutical Preparations
Fluorescent Antibody Technique
Flow Cytometry
Biomarkers
Epithelial Cells
Breast Neoplasms
Antigens
Cell Line

Keywords

  • Acetylated tubulin
  • EpCAM
  • Epothilone B
  • Hey cells
  • Taxol

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology
  • Medicine(all)

Cite this

Epothilone B enhances surface EpCAM expression in ovarian cancer Hey cells. / Shahabi, Shohreh; Yang, Chia-Ping H.; Goldberg, Gary L.; Band Horwitz, Susan.

In: Gynecologic Oncology, Vol. 119, No. 2, 11.2010, p. 345-350.

Research output: Contribution to journalArticle

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abstract = "Objectives: Epothilone B (EpoB), like Taxol, stabilizes microtubules resulting in an inhibition of microtubule dynamic instability. The drug is being evaluated in phase III clinical trials. An EpoB analog, Ixabepilone, was approved by the FDA for the treatment of taxane-resistant metastatic breast cancer. Epithelial cell adhesion antigen (EpCAM) expression is significantly higher in epithelial ovarian cancer cells compared to normal cells. The effects of EpoB and other microtubule-interacting agents on surface EpCAM expression were studied. Methods: Biochemical methods, immunofluorescence and flow cytometry were used to identify EpCAM expression on the surface of the ovarian cancer cell line, Hey, after exposure to EpoB. The relationship between EpoB-mediated surface EpCAM expression and EpoB-induced α-tubulin acetylation, a surrogate marker for stable microtubules, in Hey cells also was investigated. Results: Nanomolar concentrations of EpoB, Taxol, discodermolide or vinblastine caused a marked increase in surface EpCAM expression in Hey cells. Alpha-tubulin acetylation was increased following treatment with Taxol, EpoB and discodermolide, but not with vinblastine, indicating that drug-enhanced surface EpCAM expression does not correlate with tubulin acetylation or stabilization. Unexpectedly, EpoB did not have a significant effect on EpCAM mRNA expression, nor did it alter the level of total cellular EpCAM in Hey cells. Conclusions: The results indicate that disruption of the microtubule cytoskeleton is associated with the redistribution of cell surface antigens in ovarian cancer cells. The increase in cell surface EpCAM antigen density may facilitate the antibody targeting of EpCAM-positive ovarian cancer cells.",
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