What is it about?
Of the two classic opposing hypotheses of the orgin of the cancer cell, namely the "Stem Cell" or the "De-differentiation " or "Reprogramming" , I have challeged the current prevailing paradigm that drives 99.99% of all cancer prevention and therapy, namely I do not believe the "re-programming " hypothesis is correct. Using normal human organ-specific adult stem cells, we have shown that these adult stem cells can give rise to two very different kinds of "cancer stem cells". While both share an identical phenotype, namely, they both are unable to have functional gap junctional intercellular coimmunication, one type does express the Oct4A gene but does not express any connexin genes or connexin proteins, while the other does not express the Oct4A gene but does express the connexin gene and protein, which is rendered non-functional by some oncogene product. Therefore, neither type has functional gap junctions,which are needed for growth control, differentiation , apoptosis or senescence.
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Why is it important?
The phentypes of these two very different kinds of "cancer stem cells" will prevent a single strategy to kill both types. The first type, upon its growth, will remain as an embryonic type of tumor, whereas the second type , as it grows, changes its microenvironment in vivo, to partially differentiate into a mixture of a few "cancer stem cells , many " cancer non-stem cells", some surrounding stromal cells, and invasive immune cells.
Perspectives
Therefore, the strategies to target these two different "cancer stem cells" will be radically different. In the first case, one needs to find agents or conditions that will suppress the Oct4A gene and to express the connexin gene, its protein and have functional gap junctions to terminally differentiate , as in human testicular cancer by cisplatin. For the second type, the strategy will be extremely more complex for these heterogeneous mixture of cells in a tumor. Here , one must view the complex interacting and communicating cells as a whole. Targeting the unique "cancer stem cells" in this mixture will be extremely difficult. As the late Dr. Van R. Potter stated: "“The cancer problem is not merely a cell problem; it is a problem of cell interaction, not only within tissues, but also with distal cells in other tissues. But in stressing the whole organism, we must also remember that the integration of normal cells with the welfare of the whole organism is brought about by molecular messages acting on molecular receptors.” [Potter, V.R. (1973). Biochemistry of cancer. In Holland, J. and Frei, E (Eds.), Cancer Medicine (pp. 178-192). Philadelphia: Lea, E. and Febiger. ]
Prof essor James E Trosko
Michigan State University
Read the Original
This page is a summary of: Are We Still Missing the Target in Trying to Prevent and Treat Human Cancers?, Novel Approaches in Cancer Study, August 2019, Crimson Publishers,
DOI: 10.31031/nacs.2019.03.000556.
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