Putative cancer stem cells in malignant pleural mesothelioma show resistance to cisplatin and pemetrexed

Cortes-Dericks, Lourdes; Carboni, Giovanni L; Schmid, Ralph A; Karoubi, Golnaz (2010). Putative cancer stem cells in malignant pleural mesothelioma show resistance to cisplatin and pemetrexed. International journal of oncology, 37(2), pp. 437-44. Athens: Spandidos Publications 10.3892/ijo_00000692

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Malignant pleural mesothelioma (MPM) is a lethal cancer of the mesothelium with high chemotherapeutic resistance via unknown mechanisms. A prevailing hypothesis states that cancer stem cells (CSCs) persist in tumors causing relapse after chemotherapy, thus, rendering these cells as critical targets responsible for tumor resistance and recurrence. We selected candidate CSC markers based on expansion under hypoxic conditions, a hallmark for the selection of chemoresistant cells; and investigated the expression of CSC markers: CD133, Bmi-1, uPAR and ABCG2 in three MPM cell lines and normal mesothelial cells by quantitative RT-PCR. Furthermore, we evaluated the chemotherapeutic resistance associated with each CSC marker by determining the change in CSC marker-mRNA levels as an index of drug-resistance following treatment with either cisplatin or pemetrexed. We demonstrate the expression of CSC markers: CD133, Bmi-1, uPAR and ABCG2 in both normal and MPM cell lines. Bmi-1+, uPAR+ and ABCG2+ cells show a distinct role in conferring chemoresistance to cisplatin and pemetrexed in the malignant setting. By contrast, these markers have no apparent participation in chemoresistance to drug treatments in normal mesothelial cells. Intriguingly, CD133 revealed chemoresistant properties in both normal mesothelial and malignant pleural mesothelioma cells. This study provides evidence of putative CSCs conferring drug-resistance to cisplatin and pemetrexed in MPM cell lines. Specific targeting of these drug-resistant cells, while considering the functional heterogeneity of the MPM subtypes, may contribute to more focused and effective chemotherapeutic regimens for malignant pleural mesothelioma.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Thoracic Surgery

UniBE Contributor:

Cortes-Dericks, Lourdes; Carboni, Giovanni Luca; Schmid, Ralph and Karoubi, Golnaz

ISSN:

1019-6439

Publisher:

Spandidos Publications

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:08

Last Modified:

04 May 2014 23:04

Publisher DOI:

10.3892/ijo_00000692

PubMed ID:

20596671

Web of Science ID:

000280024500022

URI:

https://boris.unibe.ch/id/eprint/331 (FactScience: 197594)

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