Next Article in Journal
Differential MicroRNA Landscape Triggered by Estrogens in Cancer Associated Fibroblasts (CAFs) of Primary and Metastatic Breast Tumors
Next Article in Special Issue
Lentiviral Vectors as Tools for the Study and Treatment of Glioblastoma
Previous Article in Journal
Safety and Usefulness of Cryobiopsy and Stamp Cytology for the Diagnosis of Peripheral Pulmonary Lesions
Previous Article in Special Issue
Allergic Signs in Glioma Pathology: Current Knowledge and Future Perspectives
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessArticle

Dysregulation of Macropinocytosis Processes in Glioblastomas May Be Exploited to Increase Intracellular Anti-Cancer Drug Levels: The Example of Temozolomide

Department of Pharmacotherapy and Pharmaceuticals, Faculty of Pharmacy, Université Libre de Bruxelles (ULB), 1050 Brussels, Belgium
RD3-Pharmacognosy, Bioanalysis and Drug Discovery Unit and Analytical Platform, Faculty of Pharmacy, Université libre de Bruxelles (ULB), 1050 Brussels, Belgium
VIB Nucleomics Core, VIB, 3000 Leuven, Belgium
Department of Cancer Biology, University of Toledo College of Medicine, Toledo, OH 43614, USA
ULB Cancer Research Center, Université libre de Bruxelles (ULB), 1050 Bruxelles, Belgium
Author to whom correspondence should be addressed.
Cancers 2019, 11(3), 411;
Received: 27 December 2018 / Revised: 15 March 2019 / Accepted: 20 March 2019 / Published: 22 March 2019
(This article belongs to the Special Issue Glioblastoma: State of the Art and Future Perspectives)
PDF [7443 KB, uploaded 28 March 2019]
  |     |  


Macropinocytosis is a clathrin-independent endocytosis of extracellular fluid that may contribute to cancer aggressiveness through nutrient supply, recycling of plasma membrane and receptors, and exosome internalization. Macropinocytosis may be notably triggered by epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (PDGFR), two well-known markers for glioblastoma aggressiveness. Therefore, we studied whether the expression of key actors of macropinocytosis is modified in human glioma datasets. Strong deregulation has been evidenced at the mRNA level according to the grade of the tumor, and 38 macropinocytosis-related gene signatures allowed discrimination of the glioblastoma (GBM) samples. Honokiol-induced vacuolization was then compared to vacquinol-1 and MOMIPP, two known macropinocytosis inducers. Despite high phase-contrast morphological similarities, honokiol-induced vacuoles appeared to originate from both endocytosis and ER. Also, acridine orange staining suggested differences in the macropinosomes’ fate: their fusion with lysosomes appeared very limited in 3-(5-methoxy -2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (MOMIPP)-treated cells. Nevertheless, each of the compounds markedly increased temozolomide uptake by glioma cells, as evidenced by LC-MS. In conclusion, the observed deregulation of macropinocytosis in GBM makes them prone to respond to various compounds affecting their formation and/or intracellular fate. Considering that sustained macropinocytosis may also trigger cell death of both sensitive and resistant GBM cells, we propose to envisage macropinocytosis inducers in combination approaches to obtain dual benefits: increased drug uptake and additive/synergistic effects. View Full-Text
Keywords: glioma; macropinocytosis; methuosis; honokiol; vacquinol-1; MOMIPP; temozolomide glioma; macropinocytosis; methuosis; honokiol; vacquinol-1; MOMIPP; temozolomide

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Colin, M.; Delporte, C.; Janky, R.; Lechon, A.-S.; Renard, G.; Van Antwerpen, P.; Maltese, W.A.; Mathieu, V. Dysregulation of Macropinocytosis Processes in Glioblastomas May Be Exploited to Increase Intracellular Anti-Cancer Drug Levels: The Example of Temozolomide. Cancers 2019, 11, 411.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top