TY - JOUR
T1 - Tunneling nanotube formation is stimulated by hypoxia in ovarian cancer cells
AU - Desir, Snider
AU - Dickson, Elizabeth L.
AU - Vogel, Rachel I.
AU - Thayanithy, Venugopal
AU - Wong, Phillip
AU - Teoh, Deanna
AU - Geller, Melissa A.
AU - Steer, Clifford J.
AU - Subramanian, Subbaya
AU - Lou, Emil
PY - 2016
Y1 - 2016
N2 - 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 cocultures 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.
AB - 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 cocultures 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.
KW - Chemoresistance
KW - Hypoxia
KW - Intercellular communication
KW - MTOR
KW - Tunneling nanotubes
UR - http://www.scopus.com/inward/record.url?scp=84978731899&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84978731899&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.9504
DO - 10.18632/oncotarget.9504
M3 - Article
C2 - 27223082
AN - SCOPUS:84978731899
SN - 1949-2553
VL - 7
SP - 43150
EP - 43161
JO - Oncotarget
JF - Oncotarget
IS - 28
ER -