Emerging role for the voltage-dependent K+ channel Kv1.5 in B-lymphocyte physiology: expression associated with human lymphoma malignancy

J Leukoc Biol. 2013 Oct;94(4):779-89. doi: 10.1189/jlb.0213094. Epub 2013 Jul 11.

Abstract

Kv, which play a role in the immune system, are remodeled during carcinogenesis. Leukocytes present a limited Kv repertoire, with Kv1.3 and Kv1.5 as isoforms that are involved in neoplastic processes, such as proliferation and migration. In this study, we identified Kv1.5 in B-lymphocytes, characterized its role in proliferation and migration, and analyzed Kv1.3 and Kv1.5 expression in human non-Hodgkin lymphomas. DLBCL, F, MCL, ALCL, and T, along with control N specimens, were analyzed. Kv1.3 and Kv1.5 were found to be remodeled differentially; whereas Kv1.3 expression did not correlate with the state of dedifferentiation or the nature of lymphomatous cells, Kv1.5 abundance correlated inversely with clinical aggressiveness. Whereas indolent F expressed noticeable levels of Kv1.5, aggressive DLBCL showed low Kv1.5 levels. In addition, control LNs expressed heterogeneous high levels of Kv1.3, which could indicate some reactivity, whereas Kv1.5 abundance was low and quite homogeneous. Our data show that Kv1.5 is a determinant of human B cell proliferation and migration, thereby identifying this channel as a new target for immunomodulation. Our work also provides new insights into the use of Kv1.3 and Kv1.5 as potential targets during tumorigenesis.

Keywords: B cell; cancer; migration; potassium channels; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • B-Lymphocytes / physiology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • Immunohistochemistry
  • Kv1.3 Potassium Channel / metabolism
  • Kv1.5 Potassium Channel / genetics
  • Kv1.5 Potassium Channel / metabolism*
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Lymphoma / genetics
  • Lymphoma / metabolism*
  • Lymphoma / pathology
  • Mice
  • Middle Aged
  • Phenotype
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Young Adult

Substances

  • KCNA5 protein, human
  • Kv1.3 Potassium Channel
  • Kv1.5 Potassium Channel
  • RNA, Messenger