Subject(s)
Alveolar Ridge Augmentation , Bone and Bones , Cortical Bone , Dental Implantation, Endosseous , HumansABSTRACT
BACKGROUND: Oesophageal squamous cell carcinoma (OSCC) is one of the leading causes of cancer-related death worldwide. However, the mechanism by which the OSCC develops remains largely unknown. Ion channels are important for cancer development. Whether the transient receptor potential canonical (TRPC), known as the non-selective cation channels, plays a role in OSCC development is unknown. METHODS: The expression of TRPC6, a member of TRPC subfamily, was examined in samples from patients with OSCC by immunostaining and in situ hybridisation. The effects of TRPC6 channels on OSCC cell cycle progression, cell growth and in vivo tumour formation were investigated. The functional TRPC6 channels were found in OSCC cells by electrophysiology and Ca(2+) imaging analysis. RESULTS: The expression of TRPC6 at protein and mRNA levels was markedly increased in human OSCC specimens than that in normal human oesophageal tissues. Blockade of TRPC6 channels in human OSCC cells inhibited elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)) and activation of Cdc2 kinase. Meanwhile, the OSCC cell cycle was arrested at G2 phase and the cell growth was suppressed. Furthermore, inhibition of TRPC6 channels suppressed in nude mice the tumour formation generated by injection of the OSCC cells. CONCLUSION: TRPC6 channels play a critical role in the development of OSCC. The [Ca(2+)](i) elevation regulated by TRPC6 channels is essential for G2 phase progression and OSCC development. These channels might be a novel target for therapeutic intervention of OSCC.
Subject(s)
Carcinoma, Squamous Cell/metabolism , Esophageal Neoplasms/metabolism , G2 Phase/physiology , TRPC Cation Channels/physiology , Animals , Carcinoma, Squamous Cell/etiology , Cell Line, Tumor , Cells, Cultured , Esophageal Neoplasms/etiology , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Mice , Mice, Nude , TRPC Cation Channels/antagonists & inhibitors , TRPC6 Cation ChannelABSTRACT
Ovarian cancer (OC) is the leading cause of death from gynecological malignancy. However, the mechanism by which OC develops remains largely unknown. Increases in cytosolic free Ca(2+) ([Ca(2+)](i)) can result in different physiological changes including cell growth, differentiation and death. The transient receptor potential (TRP) C channels are nonselective cation channels with permeability to Ca(2+). Here we report that TRPC3 channels promote human OC growth. The TRPC3 protein levels in human OC specimens were greatly increased than those in normal ovarian specimens. Downregulating TRPC3 expression in SKOV3 cells, a human OC cell line, led to reduction of proliferation, suppression in epidermal growth factor-induced Ca(2+) influx, dephosphorylation of Cdc2 and CaMKIIalpha and prolonged progression through M phase of these cells. Further, decreased the expression of TRPC3 suppressed the tumor formation generated by injecting SKOV3 cells in nude mice. Together, our results suggest that increased activity of TRPC3 channels is necessary for the development of OCs.
