2010/04/19 by Jennifer Pasquier, Pierre Magal, Pasquier, Jennifer +7 · 1 citation
Biochemistry, Genetics and Molecular Biology · Materials Science · Medicine · #Biomolecules (q-bio.BM) #Cancer therapeutics and mechanisms #Drug Transport and Resistance Mechanisms #FOS: Biological sciences #Nanoparticle-Based Drug Delivery
paper · pdf · doi:10.48550/arxiv.1004.3162
openalex publication_date 2010/04/19 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
Cancer is a proliferation disease affecting a genetically unstable cell\npopulation, in which molecular alterations can be somatically inherited by\ngenetic, epigenetic or extragenetic transmission processes, leading to a\ncooperation of neoplastic cells within tumoral tissue. The efflux protein\nP-glycoprotein (P gp) is overexpressed in many cancer cells and has known\ncapacity to confer multidrug resistance to cytotoxic therapies. Recently,\ncell-to-cell P-gp transfers have been shown. Herein, we combine experimental\nevidence and a mathematical model to examine the consequences of an\nintercellular P-gp trafficking in the extragenetic transfer of multidrug\nresistance from resistant to sensitive cell subpopulations. We report\ncell-to-cell transfers of functional P-gp in co-cultures of a P-gp\noverexpressing human breast cancer MCF-7 cell variant, selected for its\nresistance towards doxorubicin, with the parental sensitive cell line. We found\nthat P-gp as well as efflux activity distribution are progressively reorganized\nover time in co-cultures analyzed by flow cytometry. A mathematical model based\non a Boltzmann type integro-partial differential equation structured by a\ncontinuum variable corresponding to P-gp activity describes the cell\npopulations in co-culture. The mathematical model elucidates the population\nelements in the experimental data, specifically, the initial proportions, the\nproliferative growth rates, and the transfer rates of P-gp in the sensitive and\nresistant subpopulations. We confirmed cell-to-cell transfer of functional\nP-gp. The transfer process depends on the gradient of P-gp expression in the\ndonor-recipient cell interactions, as they evolve over time. Extragenetically\nacquired drug resistance is an additional aptitude of neoplastic cells which\nhas implications in the diagnostic value of P-gp expression and in the design\nof chemotherapy regimens\n