IADR Abstract Archives

Activation of mechano-sensitive ion channels in cancer cells establishes paracrine network via endothelin signaling

Abstract: Intercellular cell-cell communication of cancer cells relates to their metabolism such as, growth, progression, migration and modulation of pain. Both cancer cells and cancer-associated cells have been reported to overexpress endothelin and its receptors within cancer tissue, the autocrine and paracrine effects of endothelin axis involve in proliferation, resistance to apoptosis, migration and invasion. The detailed causes and mechanisms in releasing endothelin still remain unclear, however . We, thus, investigated the mechanical sensitivity of rat squamous cell carcinoma cells and their paracrine communication by diffusible transmitter(s) released from mechanically stimulated cells to examine endothelin system involved in cancer metabolism.Rat squamous cell carcinoma cell lines (SCC-158) were used for this study. We measured intracellular free Ca2+ concentration ( [Ca2+]i ) by fura-2/AM. [Ca2+]i changes were recorded during direct mechanical stimulation to single SCC-158 cell. For direct mechanical stimulation, glass micropipette was used to compress the cell membrane to 8 μm for 4 sec. This was done by holding the pipette for 22 sec. During direct mechanical stimulation to SCC-158, we could observe transient [Ca2+]i increases. Transient [Ca2+]i increases were also observed in neighboring cells to the stimulated SCC-158. Application of 10 μM Gd3+ and 1 μM GsMTX4 inhibited mechanical stimulation-induced [Ca2+]i increases in stimulated SCC-158. Application of 1 μM BQ-123 (endothelin A receptor inhibitor) did not inhibit [Ca2+]i increases in stimulated SCC-158 but did those in their neighboring cells.We suggest that SCC-158 express piezo-1 channel. Activation of piezo-1 channels induced endothelin release from the stimulated cells. Released endothelin then activates endothelin A receptors in the neighboring SCC-158. The results suggested that intercellular paracrine communication among cancer cells might play an important role in cancer metabolism by endothelin signaling.
Japanese Division Meeting
2020 Japanese Division Meeting (Virtual)
Virtual, Japan
2020
78
Pharmacology/Therapeutics/Toxicology
  • Ishizaki, Motoki  ( Dental Anesthesia, Tokyo Dental College, Chiyodaku, Tokyo, JAPAN )
  • Matsunaga, M.  ( D.D.S, Tokyo, JAPAN )
  • Yazaki, T.  ( dental, Edogawaaward, Tokyo, JAPAN )
  • Saito, N.  ( Dental Anesthesiology, Tokyo Dental College, Tokyo, JAPAN )
  • Ohyama, S.  ( Physiology, Tokyo Dental College, Tokyo, JAPAN )
  • Kimura, M.  ( Physiology, Tokyo Dental College, Tokyo, JAPAN )
  • Shibukawa, Y.  ( Physiology, Tokyo Dental College, Tokyo, JAPAN )
  • Ichinohe, T.  ( Dental Anesthesia, Tokyo Dental College, Chiyodaku, Tokyo, JAPAN )
  • Poster Session