Cancer Initiation: The "False Flag" hypothesis and cancer defense

Friday, March 3, 2017

The "False Flag" hypothesis and cancer defense


 In the field of psychological operations, or "psyops", a "false flag" operation is one in which a group of government backed  insurgent actors  mount an operation in order to trigger a larger operation in the opposite direction. It turns out, that "false flag" defenses exist in the molecular world too, and may in fact be as ancient as the origin of the species.
  We have previously discussed carbohydrates, or glycosylation in terms of cell-cell recognition, and argue that these systems of carbohydrate "flags" are in fact fossils from a very early phase in the evolution of life. The term "fossils", to my knowledge as first coined by Hal White in relation to nucleotide type co-enzymes that are involved in cellular respiration [1]. I have included a discussion on that hypothesis, that is "rna world" type stuff, because carbohydrate signalling, regulatory RNA and many other "non canonical" concepts are important to studying and understanding cancer progression.

  We have previously described the rattlesnake hypothesis as a system of cancer defense where by a number of protein cell surface antigens are epigenetically suppressed in somatic cells, but are expressed in cancerous cells. As triggering the immune system to distressed cells seems to be their only function, they are merely referred to in literature as cancer - testis antigens ( CTA ) , where the testis is the only other tissue where they are found in large quantity. Cancer and testis is quite a mouthful, so here we say Wingspans antigens.
  Here we describe yet another apparent cancer defense which we are going to call the "false flag" defense. In biology we usually think of bacterial cells as having large amounts of polysaccarides ( chains of sugar molecules ) on their surface , or cell wall. This is also called endotoxin, as it triggers a possibly deadly  ( sepsis ) reaction in humans and a few other mammals such as rabbits.
  The "false flag" hypothesis states that mammals such has humans also have the capability to place polysaccarides on their surface that "look like" pathogens, but the glycosyl-transferases, or enzymes used to construct these surface structures are epigenetically suppressed ( expression is blocked by DNA methylation )  in somatic cells. When the maintenance duplication of DNA methylation patterns fails, as in the case of a cancerous clone of cells, these glycosyl-transferases become expressed, and the resulting cell surface antigens are impacted.

The Forssman antigen in Streptococcus pneomoniae

  The Forssman antigen is a cell surface carbohydrate structure discovered and named for -- Forssman. It was originally discovered as a ABO type antigen on sheep blood cells. The genes for construction of the antigen are actually closely related to ABO blood type antigens. The genes associated with antigens like the Forssman antigens are called glycosyl-transferases, because they  encode amino acid sequences for enzymes which in turn are used to construct carbohydrates. In this sense, the term "glycosyl" refers to a sugar or carbohydrate molecule and "transferase" means "enzyme that moves or constructs". In the case of the Forssman antigen (Fs), the constructed carbohydrate is on the cell surface, or membrane.

Cancer and the Forssman Antigen 

Recently (2014), the Forssman Antigen has been reported to be expressed in ovarian cancer. [3]  The specific glycosyl transferase is known as GBTG1. In the words from Jacob[3]:
The GBGT1 gene encodes the globoside alpha-1,3-N-acetylgalactosaminyltransferase 1. This enzyme catalyzes the last step in the multi-step biosynthesis of the Forssman (Fs) antigen, a pentaglycosyl ceramide of the globo series glycosphingolipids.
Expression  and construction of Fs is interesting because it was previously known as an antigen that causes a spontaneous immunologic reaction in humans. That is, if shee form an l immunological reaction, or agglutinate.  What we presume here is that in cells of the body ( somatic cells ) the expression of GBTG1 is blocked by methylation of the appropriate promoter on the DNA. Thus, in the title to Jacob [3] we see the term "epigenetically regulated". Presumably then, when a clone of cancer cells looses control of its cell cycle, the appropriate DNA methylation is lost on successive generations of cells. The appropriate cancer biology term for this is "global hypomethylation" which translates to "everywhere not enough DNA methylation".

Streptococcus pneumoniae and bacterial defense

 The next important thing to known about Fs is that it is expressed in the cell wall of infectious bacteria, including streptococcus pneumoniae, the infectious agent associated with pneumococcal pneumonia, and meningitis. Since our blood reacts with this antigen, when our immune system is healthy, we are immune to this pathogen, it is a factor when a person becomes immuno-compromised. For the sake of providing some additional background on the immunological status of pneumococcus, I give you Gisch [4]. This is a pretty technical paper, but lets look at an operational term for the sake of our argument.
We here also describe for the first time that the terminal sugar residues in the pnLTA (Forssman disaccharide; α-D-GalpNAc-(1→3)-β-D-GalpNAc-(1→)), responsible for the cross-reactivity with -Forssman antigen antibodies, can be heterogeneous with respect to its degree of phosphorylcholine substitution in both O-6-positions.
What this is saying is that there is a carbohydrate ( disacharride ) which as a particular structure that  causes a reaction with the "anti-Forssman" components of blood, or antibodies. The purpose of this paper it to refine the exact structure of Fs.

The bigger picture

What we want to do now is to combine these two concepts from different areas of research, cancer research and  immunology/biochemistry and come up with a new concept. We see that the Forssman antigen is normally not expressed ( epigenetically repressed ) in tissues such as the ovary, but becomes expressed when that repression fails due to loss of control of the cell cycle. Thus, for the sake of this article, we say that the cancerous cells raise a "false flag". We call it a false flag because the immune system is already primed to launch a counter attack. The cancerous clone of cells looks like an invading infection of pneumococcus. Thus the cancer defense system is in a sense riding piggy back on the bacterial defense system. Its an economy. We might also guess that antibodies to the Forssman antigen would inhibit cancer. This too has been investigated. [5] .( Desselle, 2012)

Summary and Conclusion

Here we introduced the Forssman antigen as a carbohydrate cellular marker that is found in the prokaryot kingdom on streptococcus pneumoniae and found in human cancer cells as a result of loss of promoter methylation. The innate portion of the immune system contains an immunoglobin portion known as complement which is reactive with the Forssman antigen, and thus renders healthy individuals immune to streptococcus pneumoniae. The Forssman antigen was long thought to be absent or inactive in humans, but more recently has been found to be expressed on cancer cells as a result of loss of suppression by promoter methylation  ( epigenetic suppression ) .  The point here is that loss of suppression, presumably as a result of "global hypomethylation" leads to cancer cells which are reactive with the compliment component of the innate immune system, and as such, the immune system is activated against the cancer cells in what we refer to here as a "false flag" defense.


[1] White H.B. (1976). Coenzymes as fossils of an earlier metabolic state. Journal of Molecular Evolution,7, 101-104 [Abstract]

[2] Graf, J Glycosylaton of extra-cellular matrix proteins as fossils of an earlier metabolic state, Cancer Initiation, 2015 [here]

[3] Jacob F, Hitchins MP, Fedier A, Brennan K, Nixdorf S, Hacker NF, Ward R, Heinzelmann-Schwarz VA. Expression of GBGT1 is epigenetically regulated by DNA methylation in ovarian cancer cells. BMC Mol Biol. 2014 Oct 7;15:24. [PubMed Central]

[4]  Nicolas Gisch, Thomas Kohler, Artur J. Ulmer, Johannes Müthing,
Thomas Pribyl, Kathleen Fischer, Buko Lindner, Sven Hammerschmidt and Ulrich Zähringer
Structural Reevaluation of Streptococcus pneumoniae Lipoteichoic Acid and New
 Insights into Its Immunostimulatory Potency
May 31, 2013 The Journal of Biological Chemistry 288, 15654-15667. [JBC]

[5] Desselle A, Chaumette T, Gaugler MH, Cochonneau D, Fleurence J, Dubois N, Hulin P, Aubry J, Birkle S, Paris F. Anti-gb3 monoclonal antibody inhibits angiogenesis and tumor development. PLoS One. 2012;7(11):e45423. [PMC free article] [PubMed] 

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