Theory 13/Life, Medicine & Mind /Cancer metabolism
Symbiosis Begins at a Distance
Cells are said to switch metabolism when hypoxic. The switch may depend on how far they are from a vessel.
Metabolic symbiosis in tumours begins at a threshold distance from the vasculature, so the fraction of the tumour in symbiosis is set by vessel spacing rather than by oxygen tension alone.
01The evidence
Metabolic heterogeneity within tumours correlates with distance from vessels, and the correlation is sharper than with measured oxygen.
02The tension
Models use oxygen tension as the switch, which predicts a smooth gradient. The observed switch is sharper.
03The mechanism
Lactate produced near vessels is exported and consumed farther away, so a cell's metabolic regime depends on whether it can import lactate, which depends on the local concentration gradient set by vessel spacing.
That makes distance the determinant, and predicts a sharp transition at a spacing-dependent radius.
04What this is not
Those models use tension. This uses distance, which explains a sharper transition.
05Predictions
- P1Symbiotic fraction should track vessel spacing.
- P2The switch should be sharp.
- P3Anti-angiogenic spacing changes should shift it.
06Refutation
A smooth gradient tracking oxygen would restore the tension model.
07What it changes
It would change how metabolic targeting is dosed.