title: Highly adaptable triple-negative breast cancer cells as a functional model for testing anticancer agents.
abstract: A major obstacle in developing effective therapies against solid tumors stems from an inability to adequately model the rare subpopulation of panresistant cancer cells that may often drive the disease. We describe a strategy for optimally modeling highly abnormal and highly adaptable human triple-negative breast cancer cells, and evaluating therapies for their ability to eradicate such cells. To overcome the shortcomings often associated with cell culture models, we incorporated several features in our model including a selection of highly adaptable cancer cells based on their ability to survive a metabolic challenge. We have previously shown that metabolically adaptable cancer cells efficiently metastasize to multiple organs in nude mice. Here we show that the cancer cells modeled in our system feature an embryo-like gene expression and amplification of the fat mass and obesity associated gene FTO. We also provide evidence of upregulation of ZEB1 and downregulation of GRHL2 indicating increased epithelial to mesenchymal transition in metabolically adaptable cancer cells. Our results obtained with a variety of anticancer agents support the validity of the model of realistic panresistance and suggest that it could be used for developing anticancer agents that would overcome panresistance.
authors.affiliation: Department of Surgical Oncology, and Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Balraj
authors.initials: B
authors.lastname: Singh
authors.affiliation: Department of Surgical Oncology, and Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Anna
authors.initials: A
authors.lastname: Shamsnia
authors.affiliation: Department of Surgical Oncology, and Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Milan R
authors.initials: MR
authors.lastname: Raythatha
authors.affiliation: Department of Surgical Oncology, and Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Milligan
authors.affiliation: Department of Surgical Oncology, and Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Cady
authors.affiliation: Department of Surgical Oncology, and Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Simran
authors.initials: S
authors.lastname: Madan
authors.affiliation: Department of Surgical Oncology, and Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Anthony
authors.initials: A
authors.lastname: Lucci
mesh_terms: D000222:Adaptation, Physiological; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D055028:Comparative Genomic Hybridization; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D051379:Mice; D009765:Obesity / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011506:Proteins; D012333:RNA, Messenger; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human