title: Overexpression of the VSSC-associated CAM, β-2, enhances LNCaP cell metastasis associated behavior.
abstract: BACKGROUND
  Prostate cancer (PCa) is the second-leading cause of cancer death in American men. This is due largely to the "silent" nature of the disease until it has progressed to a highly metastatic and castrate resistant state. Voltage sensitive sodium channels (VSSCs) are multimeric transmembrane protein complexes comprised of a pore-forming α subunit and one or two β subunits. The β-subunits modulate surface expression and gating kinetics of the channels but also have inherent cell adhesion molecule (CAM) functions. We hypothesize that PCa cells use VSSC β-subunits as CAMs during PCa progression and metastasis.
  
  
  METHODS
  We overexpressed the beta-2 isoform as a C-terminal fusion protein with enhanced cyan fluorescence protein (ECFP) in the weakly metastatic LNCaP cells. The effect of beta-2 overexpression on cell morphology was examined using confocal microscopy while metastasis-associated behavior was tested by performing several in vitro metastatic functional assays and in vivo subcutaneous tumor studies.
  
  
  RESULTS
  We found that cells overexpressing beta-2 (2BECFP) converted to a bipolar fibroblastic morphology. 2BECFP cells were more adhesive than control (ECFP) to vitronectin (twofold) and Matrigel® (1.3-fold), more invasive through Matrigel® (3.6-fold in 72 hr), and had enhanced migration (2.1-fold in 96 hr) independent of proliferation in wound-healing assays. In contrast, 2BECFP cells have a reduced tumor-take and tumor volume in vivo even though the overexpression of beta-2 was maintained.
  
  
  CONCLUSIONS
  Functional overexpression of VSSC β-subunits in PCa may be one mechanism leading to increased metastatic behavior while decreasing the ability to form localized tumor masses.
authors: Laboratory for Cancer Ontogeny and Therapeutics, Department of Biological Sciences, University of Delaware, Newark, DE, USA.
authors: Keith H
authors: KH
authors: Jansson
authors: Jill E
authors: JE
authors: Lynch
authors: Nadia
authors: N
authors: Lepori-Bui
authors: Kirk J
authors: KJ
authors: Czymmek
authors: Randall L
authors: RL
authors: Duncan
authors: Robert A
authors: RA
authors: Sikes
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D053503:Epithelial Sodium Channels / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D015222:Sodium Channels / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D015815:Cell Adhesion Molecules; D053503:Epithelial Sodium Channels; D021122:Protein Subunits; D015222:Sodium Channels