Proteomics of cancer cell lines resistant to microtubule-stabilizing agents

Jakob Albrethsen, Ruth H. Angeletti, Susan Band Horwitz, Chia-Ping H. Yang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Despite the clinical success of microtubule-interacting agents (MIA), a significant challenge for oncologists is the inability to predict the response of individual patients with cancer to these drugs. In the present study, six cell lines were compared by 2D DIGE proteomics to investigate cellular resistance to the class of MIAs known as microtubule-stabilizing agents (MSA). The human lung cancer cell line A549 was compared with two drug-resistant daughter cell lines, a taxol-resistant cell line (AT12) and an epothilone B (EpoB)-resistant cell line (EpoB40). The ovarian cancer cell line Hey was compared with two drug-resistant daughter cell lines, an EpoB-resistant cell line (EpoB8) and an ixabepilone-resistant cell line (Ixab80). All 2D DIGE results were validated by Western blot analyses. A variety of cytoskeletal and cytoskeleton-associated proteins were differentially expressed in drug-resistant cells. Differential abundance of 14-3-3σ, galectin-1 and phosphorylation of stathmin are worthy of further studies as candidate predictive biomarkers for MSAs. This is especially true for galectin-1, a β-galactose-binding lectin that mediates tumor invasion and metastasis. Galectin-1 was greatly increased in EpoB- and ixabepilone-resistant cells and its suppression caused an increase in drug sensitivity in both drug-sensitive and -resistant Hey cells. Furthermore, the growth medium from resistant Hey cells contained higher levels of galectin-1, suggesting that galectin-1 could play a role in resistance to MSAs.

Original languageEnglish (US)
Pages (from-to)260-269
Number of pages10
JournalMolecular Cancer Therapeutics
Volume13
Issue number1
DOIs
StatePublished - Jan 2013

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Excipients
Microtubules
Proteomics
Galectin 1
Cell Line
Neoplasms
Two-Dimensional Difference Gel Electrophoresis
Pharmaceutical Preparations
Stathmin
Galectins
Paclitaxel
Cytoskeleton
Ovarian Neoplasms
Lung Neoplasms
Biomarkers
Western Blotting
Phosphorylation
Neoplasm Metastasis
Growth

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Proteomics of cancer cell lines resistant to microtubule-stabilizing agents. / Albrethsen, Jakob; Angeletti, Ruth H.; Band Horwitz, Susan; Yang, Chia-Ping H.

In: Molecular Cancer Therapeutics, Vol. 13, No. 1, 01.2013, p. 260-269.

Research output: Contribution to journalArticle

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