Friday, January 23, 2009

Why do tumor cells glycolyse?

Since Pasteur and Warburg it is known that tissue tends to increase glucose uptake in low oxygen environments and that tumors continue metabolizing glucose anaerobically even in presence of oxygen.
Warburg originally hypothesized that this effect not only was a hallmark of cancer but also that is was its main cause. Warburg believed that all tumor cells had malfunctioning mitochondria and thus were forced to rely on anaerobic energy metabolism.
Gatenby and Gillies recently proposed the acid mediated tumor invasion hypothesis, through which, not only glycolysis was necessary for tumor proliferation and invasion, but also that this phenotype is selected by the micronenvironment were epithelial tumors are formed.
This hypothesis proposes that the use of abundant glucose in serum anaerobically would provide enough energy for tumors to develop and also produce acicity that promotes degradation of extracellular matrix and induces apoptose in normal surrounding tissue.
One interesting point, however is that tumor do not entirely abandon aerobic metabolism. Oxygen is necessary for keeping the basic functioning of TCA cycle that not only produces energy but also is linked to production of fatty acids and and many other metabolic pathways in cells. It has been shown that tumor regions in anoxic conditions become too acid for even tumor cells to survive.
I propose that the reduction of O2 consumption in tumors is an adaptation at population level. The cells that are in tumor rim, closer to oxygen-rich tissue, consume less oxygen which diffuses through them towards the cells in the inner core of tumor, preventing excessive acidosis and allowing tumor growth.
This kind of behavior is not normally proposed in tumors, that are normally considered as a heterogenous disorganized mass, but maybe these systems of cooperation between different subpopulations in a heterogeneous environment are exactly what differentiate malignant tumors from the many neoplasias that are periodically destroyed in our bodies without our knowing.


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