Linked Life Data

18482982

Source:http://linkedlifedata.com/resource/pubmed/id/18482982

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
29
pubmed:dateCreated
2008-7-14
pubmed:abstractText
CA9 is a membrane-tethered, carbonic anhydrase (CA) enzyme, expressed mainly at the external surface of cells, that catalyzes reversible CO(2) hydration. Expression is greatly enhanced in many tumors, particularly in aggressive carcinomas. The functional role of CA9 in tumors is not well established. Here we show that CA9, when expressed heterologously in cultured spheroids (0.5-mm diameter, ~25,000 cells) of RT112 cells (derived from bladder carcinoma), induces a near-uniform intracellular pH (pH(i)) throughout the structure. Dynamic pH(i) changes during displacements of superfusate CO(2) concentration are also spatially coincident (within 2 s). In contrast, spheroids of wild-type RT112 cells lacking CA9 exhibit an acidic core (~0.25 pH(i) reduction) and significant time delays (~9 s) for pH(i) changes in core versus peripheral regions. pH(i) non-uniformity also occurs in CA9-expressing spheroids after selective pharmacological inhibition of the enzyme. In isolated RT112 cells, pH(i) regulation is unaffected by CA9 expression. The influence of CA9 on pH(i) is thus only evident in multicellular tissue. Diffusion-reaction modeling indicates that CA9 coordinates pH(i) spatially by facilitating CO(2) diffusion in the unstirred extracellular space of the spheroid. We suggest that pH(i) coordination may favor survival and growth of a tumor. By disrupting spatial pH(i) control, inhibition of CA9 activity may offer a novel strategy for the clinical treatment of CA9-associated tumors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
283
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
20473-83
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Tumor-associated carbonic anhydrase 9 spatially coordinates intracellular pH in three-dimensional multicellular growths.
pubmed:affiliation
Department of Physiology, Anatomy, and Genetics, Burdon Sanderson Cardiac Science Centre, Oxford, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't