Further notes about the morphostasis concept – split files

(08) Marrow derived stem cells and cancers

Timothy Wang's group (Massachusetts Medical School) and other workers have recently reported some interesting findings that could have far reaching implications – especially for morphostasis. Bone marrow derived cells can infiltrate a wound and take on the form of local tissue cells. Cancerous cells expressing a local cell phenotype (gastric carcinoma) were shown to be descended from a bone marrow cell line rather than from a de–differentiated and malignant local cell line. The implications for tissue homeostasis (morphostasis) are, potentially, enormous. Not only would bone marrow derived cells (monocytoid cells) infiltrate areas where tissue homeostasis is disrupted but they might also, at some stage in the "resolving" process attempt local tissue regeneration. It is becoming increasingly clear that locally persistent chronic inflammation is often the prelude to the onset of cancer and that, as inflammation subsides, the immigrant inflammatory cells go on to promote resolution and regeneration. It is tempting to speculate that cancer may be, in many cases, the occasional product of a physiological repair (homeostasis restoring) mechanism that has gone wrong. This behaviour would be consistent with the idea that macrophages are closer to free amoeboid cells in their state of differentiation than tissue resident (building block) cells. Thus, free roaming amoebocytes occupy a central "shell" in the morphostatic response. (Science Daily summary original article in Science ).

One thing that has to be dealt with, should more cancers be found to be derived from immigrant myeloid cells, is the relevance of mutations and the long antecedent history of local tissue exposure. Clearly these mutations are of importance but we may have jumped to conclusions about the exact way in which they give rise to a cancerous growth.

This leads nicely into a perspective of cancer that sees it as "distorted regeneration". Inherent in the process of morphostasis is the damage –> inflammation –> debris clearance –> regeneration sequence. To free cells of any restriction to growth (division and multiplication) it is necessary/desirable to temporarily abandon intercellular communication. To bring growth back under control and to coordinate healthy, co–ordinated differentiation amongst a group of cells, it is probably necessary/desirable to re–establish gap junctional intercellular communication. It is in the process of normal regeneration that carcinogens might facilitate this distortion. The drive to regenerate might be continuing without the system being able to "close out" (a chronic inflammatory process might be sufficient).

Once again, the morphostasis perspective opens out a view that becomes almost tautologous (inherent of the system and therefore no need to state it) whereas the old view does not inherently encapsulate it.

Grandics P. also develops a parallel concept of "The cancer stem cell: evidence for its origin as an injured autoreactive T Cell." in Mol Cancer. 2006 Feb 14;5:6.