Hypertonic saline attenuates colonic tumor cell metastatic potential by activating transmembrane sodium conductance.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Springer Country of Publication: United States NLM ID: 0211301 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0022-2631 (Print) Linking ISSN: 00222631 NLM ISO Abbreviation: J Membr Biol Subsets: MEDLINE
    • Publication Information:
      Original Publication: New York, Springer.
    • Subject Terms:
      Saline Solution, Hypertonic*; Cell Membrane/*metabolism ; Colonic Neoplasms/*metabolism ; Sodium/*metabolism; Cell Line, Tumor ; Humans ; Integrin beta1/biosynthesis ; Integrin beta1/genetics ; Neoplasm Metastasis
    • Abstract:
      Hypertonic saline (HTS) suppresses tumor cell-endothelial interactions by reducing integrin expression. This translates into reduced adhesion, migration and metastatic potential. This study determined the relative contributions of hyperosmolarity and sodium-specific hypertonicity on the inhibitory effects of HTS, the intracellular pH and sodium responses to HTS and the role of cytoskeletal remodeling in these changes. Human colonic tumor cells (LS174T) were exposed to lipopolysaccharide under isotonic, hypertonic, sodium-free (N-methyl-D-glucamine), hyperosmolar (mannitol or urea), disrupted cytoskeletal (10 microg/ml cytochalasin D) conditions or in the presence of 5-(N-ethyl-N-isopropyl)amiloride (EIPA). Beta(1) integrin expression was measured flow-cytometrically. Intracellular sodium and pH were measured with confocal laser microscopic imaging. Statistical analysis was performed with analysis of variance, and P < 0.05 was considered significant. Data are represented as mean +/- SEM. Hypertonic exposure attenuated integrin expression (62.03 +/- 4.7% of control, P < 0.04). No discernible effect was observed with sodium-free or hyperosmolar solutions. HTS evoked a cellular alkalinization (by a mean 0.2 pH units) and an increase in cytosolic sodium concentration (by a mean 12.4 mM, P < 0.001) via upregulation of sodium-hydrogen exchange. Disassembly of actin microfilaments by cytochalasin D and antiporter inhibition with EIPA abrogated the effect of hypertonicity on integrin expression and intracellular sodium and pH (P < 0.05). HTS downregulates adhesion molecule expression via a hypertonic, sodium-specific, cytoskeletally mediated mechanism that involves activation of sodium-hydrogen exchange with associated changes in intracellular pH and sodium concentrations.
    • References:
      Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):6971-5. (PMID: 1651488)
      Am J Physiol. 1991 Nov;261(5 Pt 1):C882-8. (PMID: 1659214)
      Arch Surg. 2003 Jan;138(1):9-14. (PMID: 12511143)
      Annu Rev Physiol. 1985;47:545-60. (PMID: 2581505)
      J Trauma. 1999 Apr;46(4):582-8; discussion 588-9. (PMID: 10217219)
      World J Gastroenterol. 2005 Mar 21;11(11):1577-81. (PMID: 15786530)
      Am J Physiol. 1991 Dec;261(6 Pt 1):C1154-61. (PMID: 1767817)
      Biochem Biophys Res Commun. 2004 Dec 10;325(2):595-9. (PMID: 15530434)
      Am J Physiol. 1981 Oct;241(4):G300-5. (PMID: 7315969)
      Surgery. 2005 Jan;137(1):66-74. (PMID: 15614283)
      Cell. 2000 Jan 7;100(1):57-70. (PMID: 10647931)
      Br J Cancer. 1999 Dec;81(8):1311-7. (PMID: 10604727)
      J Trauma. 2001 Feb;50(2):206-12. (PMID: 11242283)
      Surgery. 2004 Jul;136(1):76-83. (PMID: 15232542)
      Cell Physiol Biochem. 2003;13(5):257-62. (PMID: 14586169)
      J Biol Chem. 1999 Jul 30;274(31):22072-80. (PMID: 10419535)
      J Surg Res. 2001 May 1;97(1):14-9. (PMID: 11319874)
      Ann Surg. 2003 Aug;238(2):249-57. (PMID: 12894019)
      Am J Physiol Cell Physiol. 2000 Sep;279(3):C619-33. (PMID: 10942712)
      J Membr Biol. 1999 Jul 1;170(1):17-26. (PMID: 10398757)
      J Immunol. 2003 Jan 15;170(2):795-804. (PMID: 12517943)
      Crit Care Med. 2005 Jan;33(1):203-8; discussion 259-60. (PMID: 15644670)
      Am J Physiol. 1984 Nov;247(5 Pt 1):G537-41. (PMID: 6093583)
      Cell. 2004 Feb 6;116(3):457-66. (PMID: 15016379)
      Nat Med. 2000 Jan;6(1):100-2. (PMID: 10613833)
      J Biol Chem. 1999 Mar 19;274(12):8093-102. (PMID: 10075710)
      Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2538-42. (PMID: 10051678)
      Br J Surg. 1995 Aug;82(8):1060-5. (PMID: 7648154)
      Symp Soc Exp Biol. 1993;47:107-36. (PMID: 8165561)
      J Cell Physiol. 1996 Apr;167(1):60-71. (PMID: 8698841)
      Oncology. 2000 Sep;59(3):217-22. (PMID: 11053989)
      J Pathol. 2001 Oct;195(3):336-42. (PMID: 11673831)
      J Leukoc Biol. 2001 Aug;70(2):261-73. (PMID: 11493618)
      J Biol Chem. 1997 Jul 11;272(28):17303-11. (PMID: 9211867)
      J Surg Res. 2002 Sep;107(1):1-6. (PMID: 12384057)
      EMBO J. 1994 Oct 3;13(19):4440-50. (PMID: 7925286)
    • Accession Number:
      0 (Integrin beta1)
      0 (Saline Solution, Hypertonic)
      9NEZ333N27 (Sodium)
    • Publication Date:
      Date Created: 20060922 Date Completed: 20061222 Latest Revision: 20181113
    • Publication Date:
      20231215
    • Accession Number:
      10.1007/s00232-006-0011-8
    • Accession Number:
      16988862