American Association for Cancer Research
00085472can122796-sup-fig10.pdf (81.09 kB)

Supplementary Figure 10 from Acidity Generated by the Tumor Microenvironment Drives Local Invasion

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journal contribution
posted on 2023-03-30, 22:05 authored by 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

PDF file - 81K, Figure S10: Inhibition of tumor growth as a result of NaHCO3 treatment. Tumor area was measured at days 4 and 13 by fluorescent pixel number using Image-Pro Plus v6.2. The mean growth illustrated a significant increase in size of the control tumor over 2 weeks (p<0.033). In contrast, following bicarbonate treatment, the size of the tumor significantly decreased (p<0.003). Comparing control vs. bicarbonate mice on day 13 showed a significant difference (p<0.028) using three different statistical approaches.



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.

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