title: Proteomics of cancer cell lines resistant to microtubule-stabilizing agents.
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.
authors.affiliation: Corresponding Author: Chia-Ping Huang Yang, Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461. chia-ping.h.yang@einstein.yu.edu.
authors.forename: Jakob
authors.initials: J
authors.lastname: Albrethsen
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Angeletti
authors.forename: Susan Band
authors.initials: SB
authors.lastname: Horwitz
authors.forename: Chia-Ping Huang
authors.initials: CP
authors.lastname: Yang
mesh_terms: D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015180:Electrophoresis, Gel, Two-Dimensional; D034261:Epothilones / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008870:Microtubules / Q000187:drug effects*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D017239:Paclitaxel / Q000008:administration & dosage; D040901:Proteomics
chemical_list: D003598:Cytoskeletal Proteins; D034261:Epothilones; D009363:Neoplasm Proteins; D017239:Paclitaxel