Cancer Initiation: Bone Marrow Stem Cells Provide a micro-environment that evades the immune system

Thursday, February 21, 2013

Bone Marrow Stem Cells Provide a micro-environment that evades the immune system

A recent scientific announcement not immediately related to cancer may in fact have profound implications related to our understanding of cancer initiation and metastasis. It has been shown that tuberculosis bacteria can evade the immune system by "hiding" in the stem cells of the bone marrow.[1] [2]. This has profound implications in cancer research becasue these "CD271 positive" cells have also been identified as primary correlates to nucleation of cancer in bone as a result of metastasis of breast cancer cells.[3]
  The significance of "Das" is that the mechanism of "DeGiorgi" has not been elucidated. With Das, we can now hypothesize that the observatons and correlatons in De Giorgi are due to protection from the normal operation of the immune system in the micro-environment of bone marrow, particularly in association with CD271 positive hematopoetic stem cells.
 Even more importantly,  down regulation of the immune system in bone marrow has been predicted based upon what has been known as the "rattlesnake hypothesis". Briefly stated, the rattlesnake hypothesis proposes that cells of the body which must for biological, reproductive and metabolic reasons, express telomerase must also express "cancer/testes antigens". (CT antigens)
  In other words, it has long been observed and proposed that the "Hayflick Limit" operates as a native defense against cancer. The Hayflick limit is imposed by the repression due to methylation in the promoter region of telomerase. Certain cells, such as germ cells ( testes) and stem cells must express telomerase. As such, they need a different primary defense against loss of control of the cell cycle and the imitation of cancer.  In these cells, antigens known as CT antigens provide a clue to the immune system that the cell posses a particular "danger". As such expression of telomerase represents the fangs , and expression of CT antigens represents the rattle.  Thus, they hypothesis of the function of CT antigens is to serve as a flag to the immune system that the cell is expressing telomerase, and if it is not in an immune protected compartment of the body, such as the tests, the brain or bone marrow, the immune system will recognize and attack the cell.
The hypothesis explains many long observed phenomenon such as why sperm cells generate an immune response in the host, and why the brain must have a barrier and its own immune system.
[1] Nsikan Akpan Stem Cells: Safe Haven For TB The Scientist
[2] Das et al., CD271+ bone marrow mesenchymal stem cells may provide a niche for dormant Mycobacterium tuberculosis, Science Translational Medicine, 2013. [Abstract]
[3] De Giorgi et. al, Cancer Biol Ther. 2011 May 1;11(9):812-5. Epub 2011 May 1. Mesenchymal stem cells expressing GD2 and CD271 correlate with breast cancer-initiating cells in bone marrow. [Abstract]

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