Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells: A Possible New Treatment Strategy

Stem Cells International
Ninna Aggerholm-PedersenBoe Sandahl Sorensen

Abstract

Background. One of the major challenges affecting sarcoma treatment outcome, particularly that of metastatic disease, is resistance to chemotherapy. Cancer-initiating cells are considered a major contributor to this resistance. Methods. An immortalised nontransformed human stromal (mesenchymal) stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK) activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI) treatment with or without doxorubicin was assessed by MTS assay. Results. Initial results showed that the hMSC-TERT4 was more doxorubicin-sensitive while hMSC-TERT20-CE8 was less doxorubicin-sensitive evidenced by monitoring cell viability in the presence of doxorubicin at different doses. The epidermal growth factor receptor (EGFR) was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8. However, inhibition with the TKI dasatinib in ...Continue Reading

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Citations

May 31, 2017·International Journal of Molecular Sciences·Jia-Lin YangPhilip J Crowe
Jun 14, 2020·Cells·Paula Martínez-DelgadoJavier Martin-Broto
Apr 25, 2019·JCO Precision Oncology·Roberto Carmagnani PestanaVivek Subbiah
Mar 4, 2020·Cardiovascular Toxicology·Brian B Hasinoff, Daywin Patel

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Cell Signaling by Tyrosine Kinases

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