title: Cancer Cell Plasticity: Rapid Reversal of Chemosensitivity and Expression of Stemness Markers in Lung and Breast Cancer Tumorspheres.
abstract: In cancer cells, the reversible nature of the stemness status in terms of chemoresistance has been poorly characterized. In this study, we have simulated one cycle of environmental conditions to study such reversibility by first generating floating tumorspheres (FTs) from lung and breast cancer cells by culturing them in serum-free media without the addition of any external mitogenic stimulation, and subsequently (after 2 weeks) re-incubating them back in serum-containing media to simulate routine culture conditions (RCCs). We found that cancer cells are extremely plastic: cells grown under RCCs become multidrug-resistant when grown as FTs, but upon re-incubation under RCCs quickly re-attach and lose the acquired resistance. These phenotypic changes are accompanied by concomitant changes in the expression of key proteins associated with multiple pathways important for chemoresistance, survival, and stemness maintenance. Therefore, our strategy provides an excellent experimental model to study environmental factors that modulate the plasticity of cancer cells. J. Cell. Physiol. 232: 2280-2286, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Hampton University, Hampton, Virginia.
authors.forename: Juan Sebastian
authors.initials: JS
authors.lastname: Yakisich
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Hampton University, Hampton, Virginia.
authors.forename: Neelam
authors.initials: N
authors.lastname: Azad
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Hampton University, Hampton, Virginia.
authors.forename: Vivek
authors.initials: V
authors.lastname: Kaushik
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Hampton University, Hampton, Virginia.
authors.forename: Anand Krishnan V
authors.initials: AKV
authors.lastname: Iyer
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D000066670:Cell Plasticity / Q000187:drug effects*; D049109:Cell Proliferation; D016895:Culture Media, Serum-Free / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D061986:MCF-7 Cells; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D018874:Spheroids, Cellular; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016895:Culture Media, Serum-Free; D047428:Protein Kinase Inhibitors; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors