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Role of cation‐chloride cotransporter activity in glial tumor proliferation and migration
Author(s) -
Gag Kenneth B.,
Delpire Eric
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.936.2
Subject(s) - cotransporter , glioma , cell culture , cell migration , diuretic , cancer research , extracellular , chemistry , chloride channel , medicine , cell , biology , microbiology and biotechnology , sodium , biochemistry , genetics , organic chemistry
Primary central nervous system tumors account for 2.2% of all cancer‐related deaths. Glioblastoma multiformes, the most aggressive form of brain tumor have relatively short median survival times (9–12 months in most cases). Like most aggressive cancers, malignant gliomas exhibit a strong tendency to migrate through narrow extracellular spaces in brain tissue by the functional shape‐volume changes mediated by net salt fluxes across cell membranes. The electroneutral‐coupled movement of ions by the cation‐chloride cotransporter family may, therefore, have an important role in this process. In this study, we used the ‘scratch wound’ assay and time‐lapse microscopy to examine the role of cotransporter activity on the proliferation and migration of rat C6 glioma cells, an immortalized astrocytoma tumor cell line. Untreated C6 cells completely filled the ‘wound area’ within 6 hours, significantly faster than their doubling time. Application of 2 mM furosemide (loop diuretic) completely inhibited the ‘closure’ of the wound area. Four hours after removal of the loop diuretic, the C6 cells were able to migrate into the ‘wound area’, similar to untreated cells. These studies suggest a significant role for cation‐chloride cotransporter activity in the physiology of primary CNS tumors and may help identify novel targets for the development of drugs and therapies to combat these aggressive and fatal neoplasms.