title: Tunneling nanotube formation is stimulated by hypoxia in ovarian cancer cells.
abstract: In this study, we demonstrated that hypoxic conditions stimulated an increase in tunneling nanotube (TNT) formation in chemoresistant ovarian cancer cells (SKOV3, C200).We found that suppressing the mTOR pathway using either everolimus or metformin led to suppression of TNT formation in vitro, verifying TNTs as a potential target for cancer-directed therapy. Additionally, TNT formation was detected in co-cultures including between platinum-resistant SKOV3 cells, between SKOV3 cells and platinum-chemosensitive A2780 cells, and between SKOV3 cells cultured with benign ovarian epithelial (IOSE) cells; these findings indicate that TNTs are novel conduits for malignant cell interactions and tumor cell interactions with other cells in the microenvironment. When chemoresistant C200 and parent chemosensitive A2780 cells were co-cultured, chemoresistant cells displayed a higher likelihood of TNT formation to each other than to chemosensitive malignant or benign epithelial cells. Hypoxia-induced TNT formation represents a potential mechanism for intercellular communication in ovarian cancer and other forms of invasive refractory cancers.
authors.affiliation: Integrative Biology and Physiology Program, University of Minnesota, Minneapolis, MN, USA.|Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Snider
authors.initials: S
authors.lastname: Desir
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Dickson
authors.affiliation: Biostatistics and Bioinformatics Core, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Rachel I
authors.initials: RI
authors.lastname: Vogel
authors.affiliation: Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Venugopal
authors.initials: V
authors.lastname: Thayanithy
authors.affiliation: Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Wong
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Deanna
authors.initials: D
authors.lastname: Teoh
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Geller
authors.affiliation: Departments of Medicine and Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Steer
authors.affiliation: Department of Surgery, Division of Basic Science and Translational Research, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Subbaya
authors.initials: S
authors.lastname: Subramanian
authors.affiliation: Integrative Biology and Physiology Program, University of Minnesota, Minneapolis, MN, USA.|Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Emil
authors.initials: E
authors.lastname: Lou
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001692:Biological Transport; D002450:Cell Communication; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D018920:Coculture Techniques; D019008:Drug Resistance, Neoplasm; D000068338:Everolimus / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000473:pathology*; D007365:Intercellular Junctions / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D008687:Metformin / Q000627:therapeutic use; D018613:Microscopy, Confocal; D036641:Microscopy, Fluorescence, Multiphoton; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D008687:Metformin; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: chemoresistance; hypoxia; intercellular communication; mTOR; tunneling nanotubes