Document Detail

Acidity generated by the tumor microenvironment drives local invasion.
MedLine Citation:
PMID:  23288510     Owner:  NLM     Status:  MEDLINE    
The pH of solid tumors is acidic due to increased fermentative metabolism and poor perfusion. It has been hypothesized that acid pH promotes local invasive growth and metastasis. The hypothesis that acid mediates invasion proposes that H(+) diffuses from the proximal tumor microenvironment into adjacent normal tissues where it causes tissue remodeling that permits local invasion. In the current work, tumor invasion and peritumoral pH were monitored over time using intravital microscopy. In every case, the peritumoral pH was acidic and heterogeneous and the regions of highest tumor invasion corresponded to areas of lowest pH. Tumor invasion did not occur into regions with normal or near-normal extracellular pH. Immunohistochemical analyses revealed that cells in the invasive edges expressed the glucose transporter-1 and the sodium-hydrogen exchanger-1, both of which were associated with peritumoral acidosis. In support of the functional importance of our findings, oral administration of sodium bicarbonate was sufficient to increase peritumoral pH and inhibit tumor growth and local invasion in a preclinical model, supporting the acid-mediated invasion hypothesis. Cancer Res; 73(5); 1524-35. ©2012 AACR.
Veronica Estrella; Tingan Chen; Mark Lloyd; Jonathan Wojtkowiak; Heather H Cornnell; Arig Ibrahim-Hashim; Kate Bailey; Yoganand Balagurunathan; Jennifer M Rothberg; Bonnie F Sloane; Joseph Johnson; Robert A Gatenby; Robert J Gillies
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-03
Journal Detail:
Title:  Cancer research     Volume:  73     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-05     Completed Date:  2013-04-26     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1524-35     Citation Subset:  IM    
Copyright Information:
©2012 AACR.
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MeSH Terms
Drugs, Chinese Herbal
Hydrogen-Ion Concentration*
Mice, SCID
Models, Biological
Neoplasm Invasiveness*
Neoplasms / metabolism*,  pathology*
Sodium Bicarbonate / pharmacology
Tumor Microenvironment*
Grant Support
R01 CA 077575/CA/NCI NIH HHS; R01 CA 131990S/CA/NCI NIH HHS; R01 CA077575/CA/NCI NIH HHS; R01 CA131990/CA/NCI NIH HHS; U54 CA143970/CA/NCI NIH HHS; U54 CA143970/CA/NCI NIH HHS
Reg. No./Substance:
0/Drugs, Chinese Herbal; 0/yun-chang; 8MDF5V39QO/Sodium Bicarbonate

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