Functional activity of voltage-gated sodium channels (VGSC) has been associated to the invasion and metastasis behaviors of prostate, breast, and some other types of cancer. We previously reported the functional expression of VGSC in primary cultures and biopsies derived from cervical cancer (CaC). Here, we investigate the relative expression levels of VGSC subunits and its possible role in CaC. Quantitative real-time PCR revealed that mRNA levels of Na(V) 1.6 α-subunit in CaC samples, was ~40-fold higher than in non-cancerous cervical (NCC) biopsies. A Na(V) 1.7 α-subunit variant also showed increased mRNA levels in CaC (~20-fold). All four Na(V) β subunits were also detected in CaC samples, being Na(V) β1 the most abundant. Proteins of Na(V) 1.6 and Na(V) 1.7 α-subunits were immunolocalized in both NCC and CaC biopsies and in CaC primary cultures as well; however, while in NCC sections proteins were mainly relegated to the plasma membrane, in CaC biopsies and primary cultures the respective signal was stronger and widely distributed in both cytoplasm and plasma membrane. Functional activity of Na(V) 1.6 channels in the plasma membrane of CaC cells was confirmed by whole-cell patch-clamp experiments using Cn2, a Na(V) 1.6 specific toxin, which blocked ~30% of the total sodium current. Blocking of VGSC with TTX and Cn2, did not affect proliferation neither migration, but reduced by ~20% the invasiveness of CaC primary culture cells in vitro assays. We conclude that Na(V) 1.6 is up-regulated in CaC and could serve as a novel molecular marker for the metastatic behavior of this carcinoma.

Copyright © 2011 UICC.

PMID: 21630263 [PubMed - as supplied by publisher] Source: National Library of Medicine.