Voltage-gated sodium channel expression and potentiation of human breast cancer metastasis
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Date
2005
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Abstract
Purpose: Ion channel activity is involved in several basic cellular behaviors that are integral to metastasis (e.g., proliferation, motility, secretion, and invasion), although their contribution to cancer progression has largely been ignored. The purpose of this study was to investigate voltage-gated Na + channel (VGSC) expression and its possible role in human breast cancer. Experimental Design: Functional VGSC expression was investigated in human breast cancer cell lines by patch clamp recording. The contribution of VGSC activity to directional motility, endocytosis, and invasion was evaluated by in vitro assays. Subsequent identification of the VGSC α-subunit(s) expressed in vitro was achieved using reverse transcription-PCR, immunocytochemistry, and Western blot techniques and used to investigate VGSCα expression and its association with metastasis in vivo. Results: VGSC expression was significantly up-regulated in metastatic human breast cancer cells and tissues, and VGSC activity potentiated cellular directional motility, endocytosis, and invasion. Reverse transcription-PCR revealed that Na v1.5, in its newly identified "neonatal" splice form, was specifically associated with strong metastatic potential in vitro and breast cancer progression in vivo. An antibody specific for this form confirmed up-regulation of neonatal Na v1.5 protein in breast cancer cells and tissues. Furthermore, a strong correlation was found between neonatal Na v1.5 expression and clinically assessed lymph node metastasis. Conclusions: Up-regulation of neonatal Na v1.5 occurs as an integral part of the metastatic process in human breast cancer and could serve both as a novel marker of the metastatic phenotype and a therapeutic target.
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Keywords
Ion channel, Voltage gated sodium channel
Turkish CoHE Thesis Center URL
Fields of Science
Citation
362
WoS Q
Q1
Scopus Q
Q1
Source
Volume
11
Issue
15
Start Page
5381
End Page
5389