Contribution of tumor endothelial cells to drug resistance: anti-angiogenic tyrosine kinase inhibitors act as p-glycoprotein antagonists View Full Text


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Article Info

DATE

2017-04-07

AUTHORS

MariaRosa Bani, Alessandra Decio, Raffaella Giavazzi, Carmen Ghilardi

ABSTRACT

Tumor endothelial cells (TEC) differ from the normal counterpart, in both gene expression and functionality. TEC may acquire drug resistance, a characteristic that is maintained in vitro. There is evidence that TEC are more resistant to chemotherapeutic drugs, substrates of ATP-binding cassette (ABC) transporters. TEC express p-glycoprotein (encoded by ABCB1), while no difference in other ABC transporters was revealed compared to normal endothelia. A class of tyrosine kinase inhibitors (TKI), used as angiostatic compounds, interferes with the ATPase activity of p-glycoprotein, thus impairing its functionality. The exposure of ovarian adenocarcinoma TEC to the TKIs sunitinib or sorafenib was found to abrogate resistance (proliferation and motility) to doxorubicin and paclitaxel in vitro, increasing intracellular drug accumulation. A similar effect has been reported by the p-glycoprotein inhibitor verapamil. No beneficial effect was observed in combination with cytotoxic drugs that are not p-glycoprotein substrates. The current paper reviews the mechanisms of TEC chemoresistance and shows the role of p-glycoprotein in mediating such resistance. Inhibition of p-glycoprotein by anti-angiogenic TKI might contribute to the beneficial effect of these small molecules, when combined with chemotherapy, in counteracting acquired drug resistance. More... »

PAGES

233-241

References to SciGraph publications

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  • 2013-09-24. Cancer drug resistance: an evolving paradigm in NATURE REVIEWS CANCER
  • 2008-06-05. Isolation of endothelial cells from fresh tissues in NATURE PROTOCOLS
  • 2009-12-11. Anti-angiogenic tyrosine kinase inhibitors: what is their mechanism of action? in ANGIOGENESIS
  • 2009-03-03. Cediranib (recentin, AZD2171) reverses ABCB1- and ABCC1-mediated multidrug resistance by inhibition of their transport function in CANCER CHEMOTHERAPY AND PHARMACOLOGY
  • 2008-04-30. Identification of novel vascular markers through gene expression profiling of tumor-derived endothelium in BMC GENOMICS
  • 2016-02-15. Tumor angiogenesis—characteristics of tumor endothelial cells in INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
  • 1999-08. Phenotypic and functional characteristics of tumour-derived microvascular endothelial cells in CLINICAL & EXPERIMENTAL METASTASIS
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s10456-017-9549-6

    DOI

    http://dx.doi.org/10.1007/s10456-017-9549-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1084518306

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28389777


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