Abstract：
: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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Estrella V,Chen T,Lloyd M,Wojtkowiak J,Cornnell HH,Ibrahim-Hashim A,Bailey K,Balagurunathan Y,Rothberg JM,Sloane BF,Johnson J,Gatenby RA,Gillies RJdoi
10.1158/0008-5472.CAN-12-2796subject
Has Abstractpub_date
2013-03-01 00:00:00pages
1524-35issue
5eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-12-2796journal_volume
73pub_type
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