The Warburg effect produces an acidic micro environment of cancer while still at the cellular level. This compromises the Tight Endothelial Junctions (TEJ) of the normal native vasculature creating “vasogenic edema “ which is detectable by MREPT or MREIT etc.
It is not the Warburg effects that creates the extracellular acidity but the incressed production of CO2.
This said, extracellular acidity csn be easily prevented by associating a carbonic anhydrase inhibitor such as acetazolamide with proton pump inhibitors such as lansoprazole and NHE1 inhibitors such as amiloride.
Early inhibition of NHE1 prevents cancerization.
Is an acidic micro environment a “sine qua non” of the initiation of cancer while still at the cellular level? If so, does the acidic micro environment compromise the Tight Endothelial Junctions of the normal native vasculature allowing plasma to leak? Can this “vasogenic edema “ be detected by MRI? Can the detectable image guide minimally invasive ablation of cancer while still only cellular, before tumor mass inhibits diffusion, and much before the formation of abnormal tumor vasculature creates “washout “? Will all this preclude the development of clinically significant cancer? Could this approach provide cancer screening and suppression without the use of Gadolinium chelate contrast and without the use of ionizing radiation?
Acidic microenvironment is not a sine qua non for cancerization. Intracellular alkalinization is.
When the tumor is at a very initial stage of only a few cells, intracellular alkalinization is achieved by an activated NHE1.
At this stage there is no extracellular acidity because the buffer systems and circulatory clearance of protons impede this to happen. Acidity in earnest is a step beyond and coincides with the moment in which the tumor becomes hypoxic because vascular clearance of protons becomes inefficient.
If you study a tumor which is less than 0.4 cc you will see that extracellular substance is not acidic. After that volume acidity starts to develop.
You cannot study this in a Petri dish. Only in tumors studied in vivo can be detected.
Thank you for your contribution to my understanding. I am a clinical radiologist concerned with in vivo detection and ablation of tumors. Can I assume that an acidic micro environment occurs in tumors that are greater than .4 cc in volume? Does the tumor exceed the oxygen supply at this volume?
You are right. When the tumor exceeds 0.4 cc volume oxygen supply is insufficient. That is the point where HIF-1 alpha (Hypoxia inducible factor) is activated (or better said released from VHL (Von Hippel Lindau protein). It is HIF that induces the Warburg effect. The volume of 0.4 was determined by Judah Folkman. I supose that this volume does not apply to all tumors, but some. However, what is important is the concept that there is a threshold, Beyond the threshold is when we can find Warburg effect and extracellular acidification.
Another important concept is that Warburg effect and extracellular acidification are parallel processes. However, at a certain point the excess of lactate produced by glycolysis increases extracellular acidity.
Tumors that are engeneered impeding lactate production, are still showing extracellular acidity. This means that lactate from the Warburg effect is not the main cause of extracellular acidity but a complementary factor.
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