Question

Figure 1. Lactate metabolism in tumors: a simplified cartoon showing lactate being shuttled to and from cancer cells and its potential role as a signaling molecule in driving angiogenesis. Increasing pyruvate inhibits formation of 2- oxoglutarate, with the net effect of less degradation of HIF-1a in the proteasome and increased VEGF and angiogenesis. Note that pyruvate can be increased by hypoxia "backing up" the TCA cycle, or by importation of lactate via MCTis. Some lactate shuttling likely is present between cancer cells and (1) other cancer cells within the tumor, (2) tumor stromal cells, and/or (3) non-tumor cells both local and distant from the tumor. Note that the traditional "Warburg Effect" describes tumors relying heavily on glucose uptake (via GLUTS) with subsequent lactate exportation (via MCT45) in normoxia. A "Reverse Warburg Effect" describes lactate production from stromal cells, which is then taken up and used by local cancer cells. Some unique combination of these pathways is likely present within each tumor, highlighting the need for further in vivo experimentation. (Note that MCTS can transport lactate either direction; MCTs are typically expressed in cells importing lactate, while MCT4s are expressed in cells exporting lactate.)
based on this information , how does lactate influence angiogenisis in tumors ??

thank you in advance

Answer 1

• Lactate influence angiogenesis by stimulating VEGF by activating 2 receptors in endothelial cells.
• Lactate released from tumour endothelial cells through MCT4 stimulate angiogenesis and tumour growth.
• MCTs of SLC16A gene family influences lactae availability and pH balance within the tumour.
• Elevated lactose level is a good indicator of increased glycolytic adaptation of tumours.
• It is used to intiate signalling and as a fuel by glucose deprived tumour cells.
• It inhibit PHD-2 activity thereby facilitating the action of NFkB pathway, by direct competition between lactate and PHD cosubstrate 2 oxoglutarate leading to accumulation of IKK.
• Major target of NFkB is IL-8 by using siRNA.
• anti IL-8 could prevent angiogenesis thus reducing the tumour growth.
  Glucose glucose NADPH PPP lipids glucose 6 P Ribose 5 phosphate NAD+ АТР NADHV 3-phosphoglycerate PEP glutamate-glutamine, glutamine alpha keto glutrate GSH NAD+ NADH ATP lact- lactate Pyruvate ate LDH-4 PDK Aceyl COA PDH TCA cycle NADPH