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Acidity Generated by the Tumor Microenvironment Drives Local Invasion
Cancer research (Chicago, Ill.), 2013-03, Vol.73 (5), p.1524-1535
ESTRELLA, Veronica
TINGAN CHEN
JOHNSON, Joseph
GATENBY, Robert A
GILLIES, Robert J
LLOYD, Mark
WOJTKOWIAK, Jonathan
CORNNELL, Heather H
IBRAHIM-HASHIM, Arig
BAILEY, Kate
BALAGURUNATHAN, Yoganand
ROTHBERG, Jennifer M
SLOANE, Bonnie F
2013
Details
Autor(en) / Beteiligte
ESTRELLA, Veronica
TINGAN CHEN
JOHNSON, Joseph
GATENBY, Robert A
GILLIES, Robert J
LLOYD, Mark
WOJTKOWIAK, Jonathan
CORNNELL, Heather H
IBRAHIM-HASHIM, Arig
BAILEY, Kate
BALAGURUNATHAN, Yoganand
ROTHBERG, Jennifer M
SLOANE, Bonnie F
Titel
Acidity Generated by the Tumor Microenvironment Drives Local Invasion
Ist Teil von
Cancer research (Chicago, Ill.), 2013-03, Vol.73 (5), p.1524-1535
Ort / Verlag
Philadelphia, PA: American Association for Cancer Research
Erscheinungsjahr
2013
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
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.
Sprache
Englisch
Identifikatoren
ISSN: 0008-5472
eISSN: 1538-7445
DOI: 10.1158/0008-5472.can-12-2796
Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3594450
Format
–
Schlagworte
Animals
,
Antineoplastic agents
,
Biological and medical sciences
,
Drugs, Chinese Herbal
,
Humans
,
Hydrogen-Ion Concentration
,
Medical sciences
,
Mice
,
Mice, SCID
,
Models, Biological
,
Neoplasm Invasiveness
,
Neoplasms - metabolism
,
Neoplasms - pathology
,
Pharmacology. Drug treatments
,
Sodium Bicarbonate - pharmacology
,
Tumor Microenvironment
,
Tumors
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