Usually cancer cells produce higher amount of lactate. But can it be useful for the cancer cells and how the cancer cells utilize the lactate?
MCT proteins are a set of monocarboxylate transporters (MCT) that can transport lactate. That's how intracellular lactate comes outside the cell. One important purpose of lactate is to make the extracellular environment acidic (in addition to protons exported by proton pumps).
Lower pH (acidic) activates a lot of cytokines from the extracellular matrix either by activating MMPs or by activating other proteases. These cytokines in turn mediate neovascularization, cell survival and EMT to help cancer cells.
We recently discovered the importance of lactate in resurrection of cancer stem cells "after apoptosis", explaining how lactate might help the survival of cancer (stem) cells after apoptosis through blebbishield emergency program
We had clearly examined lactate and proton pumps in the context of resurrection after apoptosis.
https://www.researchgate.net/publication/233742776_Blebbishields_the_Emergency_Program_for_Cancer_Stem_Cells_Sphere_Formation_and_Tumorigenesis_after_Apoptosis
Article Blebbishields, the Emergency Program for Cancer Stem Cells: ...
MCT proteins are a set of monocarboxylate transporters (MCT) that can transport lactate. That's how intracellular lactate comes outside the cell. One important purpose of lactate is to make the extracellular environment acidic (in addition to protons exported by proton pumps).
Lower pH (acidic) activates a lot of cytokines from the extracellular matrix either by activating MMPs or by activating other proteases. These cytokines in turn mediate neovascularization, cell survival and EMT to help cancer cells.
We recently discovered the importance of lactate in resurrection of cancer stem cells "after apoptosis", explaining how lactate might help the survival of cancer (stem) cells after apoptosis through blebbishield emergency program
We had clearly examined lactate and proton pumps in the context of resurrection after apoptosis.
https://www.researchgate.net/publication/233742776_Blebbishields_the_Emergency_Program_for_Cancer_Stem_Cells_Sphere_Formation_and_Tumorigenesis_after_Apoptosis
Article Blebbishields, the Emergency Program for Cancer Stem Cells: ...
Tumors contain aerobic and hypoxic regions that utilize different metabolic pathways to provide cellular energy to highly active malignant cells.
Metabolism is altered in the hypoxic regions; cancerous cells in these microenvironments favor more anaerboic conditions; heavy use of glycolysis followed by lactate acid formation. Lactate acid formation is characterized by ATP production and metabolite lactate;
Lactate production by cancerous cells is associated with one of the hallmarks of cancer: warburg effect.
Lactate must thus be thought of as a byproduct cellular respiration in hypoxic regions; with glucose in these regions ultimately being converted into lactate to provide cellular energy.
Moreover, this results in an acidic tumormicroenvironment which impairs several immune functions.
it might be useful to read this paper:
Choi SY, Collins CC, Gout PW, Wang Y. Cancer-generated lactic acid: a regulatory, immunosuppressive metabolite? J Pathol 2013 Aug; 230(4): 350-5 (Epub May 31, 2013). PMID: 23729358
See the following Review Article.
Metabolic reprogramming: the emerging concept and associated therapeutic strategies
Metabolic symbiosis between epithelial cancer cells and CAFs requires that each cell express a different subtype of monocarboxylate transporter (MCT). Epithelial cancer cells express MCT1, which contributes to uptake of lactate provided by caveolin1-null CAFs expressing MCT4. Tumor cells synthesize pyruvate from lactate, providing the TCA cycle with an intermediate metabolite. Notably, an extracellular space rich in lactate reflects acidic conditions, which in turn lead to the formation of pseudo-hypoxic conditions.
It should be emphasized, however, that this reverse Warburg effect is not necessarily present in all tumor types. Tumors expressing high levels of MCT4 or mesenchymal phenotype do not tend to exhibit the reverse Warburg phenomenon. Instead, cancer cells exhibit hierarchical metabolic heterogeneity: MCT4-expressing tumor cells perform glycolysis and secrete lactate via MCT4, whereas MCT1-expressing cells import lactate via MCT1 and perform OXPHOS. In addition, the amount of glucose uptake is lower in MCT1-positive cancer cells than in MCT4-positive cells. This metabolic heterogeneity is referred to as metabolic symbiosis, and this kind of lactate shuttle is also observed between neurons and astrocytes in the normal brain tissue. It is notable that normal and cancerous tissues share finely regulated mechanisms of metabolic symbiosis.
http://jeccr.biomedcentral.com/articles/10.1186/s13046-015-0221-y
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