Role of E-cadherin in the induction of apoptosis of HPV16-positive CaSki cervical cancer cells during multicellular tumor spheroid formation |
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Authors: | Takeshi Haga Noboru Uchide Sharof Tugizov Joel M Palefsky |
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Institution: | (1) Department of Veterinary Microbiology, University of Miyazaki, 1-1 Gakuen-Kibanadai-Nishi, Miyazaki 889-2192, Japan;(2) Department of Medicine, University of California, San Francisco, CA, USA |
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Abstract: | Multicellular tumor spheroids (MCTS) are three dimensional cell culture systems induced by suspension culture. MCTS are widely
used in cancer research because of their similarity to solid tumors. CaSki cells are derived from a metastatic cervical cancer
containing human papillomavirus 16 (HPV16). Cell death of CaSki cells in MCTS has been previously reported, and our model
is used to better characterize the mechanisms of cell death of HPV16-positive keratinocytes. In this study, we found that
apoptosis of CaSki cells was induced by suspension culture along with the formation of MCTS after 24 h of incubation. In suspended
CaSki cells, monoclonal antibodies blocking E-cadherin function inhibited MCTS formation and suppressed suspension-induced
apoptosis in a dose-dependent manner. Western blot for E-cadherin detected upregulation of the authentic 120 kDa band from
MCTS of CaSki cells as well as a shorter 100 kDa band. Addition of EGF, whose receptor is known to form a complex with E-cadherin,
abrogated apoptosis of suspended CaSki cells in a dose-dependent manner. These findings suggest that E-cadherin-dependent
cell–cell contact, directly or indirectly, mediates the signal to undergo apoptosis of CaSki cells during MCTS formation,
and thus provides new information on the role of E-cadherin in cervical cancer cell apoptosis. |
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Keywords: | Apoptosis E-cadherin Spheroid Cervical cancer CaSki cell EGF |
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