Further notes about the morphostasis concept – split files

(10) Cancer and morphostasis

Here are a few thoughts on where we might be heading in the future.

• Stem cells that help in the regeneration of disrupted tissues probably adopt a wandering and invasive existence and, for a short time, drop their contact inhibition (this is likely to be associated with a reduction or even withdrawal of gap junctional communication while the necessary local "invasion" into the surrounding tissues occurs. Angiogenesis is accompanied by a tightening of local endothelial cell junctions (inflammation is inhibited).
• Cancers are likely to be made up of a small population of stem cells (the "dangerous" ones) and a much bigger population of more differentiated – though abnormal – cells. Normal tissue surveillance mechanisms would have no trouble in recognising the latter as "not quite right" (to take appropriate action) if it wasn't for the positive and increasing focal immunosuppression that helps switch off aggressive immune cell surveillance and aggression. The presence of large numbers of clearly abnormal cells (distorted, triploid etc) is probably a reflection of the failure to clear not–so–healthy cells.
• Successful regeneration probably requires a temporary down regulation of auto–rejection to allow the wandering, detached stem cells to start the regenerative process without being treated as threats to tissue homeostasis. So, the down–regulation of immune scrutiny that follows on shortly after debris clearance, is a necessary phase to avoid attacking detached (but clearly useful) cells.
• Stem cells that have acquired oncogenic mutations do not close out their regenerative cycle as they should and the immune suppression is prolonged and even heightened. The local tissue microenvironment now allows the emergence of an expanding (but corrupt) stem cell population that cannot complete a normal "I've completed my job" termination signal because normal tissue stability has not been restored.
• To some degree, the evolution of progressively more potent "escapees" may occur and worsen matters but it this is just an unfortunate chance outcome rather than a "purposeful survival of the fittest".
• The emergence of adaptive immunity (B–cells/T–cells and antibodies) during evolution was accompanied by a marked impairment of wide ranging regenerative capacity. Fibrotic scarring becomes a common alternative strategy. A rising incidence of cancers – particularly carcinomas – accompanies the evolutionary emergence of adaptive immunity. The two are clearly linked but the "reasons" for this remain obscure and are the subject of much speculation.