Tumorigenesis: Actions to initiate the cancer state.
The Cell Recognition Factor theory of cancer maintains that detachment of a cell from its neighbors is necessary for most cancers to arise. After that, a malfunction or replenishment of the telomere, or a reversion to stem cell, is necessary to permit the growth of cancer cells. The immune system then comes into play in keeping cancer cells in check or in promoting their elimination. A daughter cell has three additional hurdles to overcome on its road to cancer. It must eliminate the threat of apoptosis; eliminate telomere degradation; and, prevent itself from ending up in an inhospitable environment away from resources.
I. Stem cell (immortal)
. a. Detach from neighbors
. b. Escape from Immune Surveillance
II. Daughter cell (specialized, mortal)
. a. Detach from neighbors
. b. Escape from Immune Surveillance
. c. Prevent Apoptosis
. d. Stop Degradation of the Telomere
. e. Prevent displacement into the environment (for example, epithelial cells
sloughing off into the GI tract)
Detachment refers to the loss of cell recognition factors (CRF's). If it remains attached, it means that the cell will continue to function in its original capacity. Detachments are usually the result of environmental factors that denature the adhesive molecules on their membranes but can result from genetic or epigenetic changes that alter the correct CRF expression for that cell type. Detachment is necessary because while the cell is attached, the genome is frozen in a particular stage-specific state. It is only through detachment that the genome is free to engage in reprogramming. Unfortunately, in an adult, the reprogramming that occurs creates a cell looking for stimuli that are no longer in play (those of the embryonic environment).
Why does a cell revert to such an early time period in development? The reason is that the adult cell is the end stage of the process, and any earlier cell type is just embryonic.
At an embryonic period, most cells are migratory and malleable; capable of taking on the characteristics of whatever adult cell type was required for that area of the developing organism that they happened to be in. However, they can only do this if the other cells in the area have not yet reached the adult stage. Once the adult specification is set, no embryonic cell has the mechanism to change into that adult cell type. The options are to die as a result of apoptosis or immune surveillance.
Apoptosis is that process which results in the death of the cell when certain conditions are right. The cell undergoing apoptosis self-destructs based on its own determination or on the orders of an immune cell. Apoptosis is not seen extensively in embryonic tissue for two reasons. First, the degradation of cells could create an environment that may interfere with development. Second, embryonic cells can easily reprogram themselves according to where they happen to be. If they lose contact with their neighbors, they can reprogram instead of self-destructing. While the embryonic state is in play, the right CRF's are available. It is only when the adult state is reached that cells could end up in a limbo state whenever they lose contact with neighbors and begin to express CRF's that are no longer expressed by any of the neighboring cells. [I developed the CRF theory based on the work of a female researcher in the '60's or '70's who took cancer cells and reverted them to normal by putting them in an embryonic environment.]
Immune Surveillance Avoidance means that immune cells are not getting close enough to the cell to initiate killing functions, or that immune cells are dysfunctional. This would partly explain the high prevalence of epithelial cell cancers. Immune cells typically respond to deeper invasions that break through the barrier imposed by epithelial cells. If an immune cell were to get too close to the exterior (or the inside of the gut), it would very likely respond with an unnecessary attack for it would very likely encounter antigens that would trigger it into action. The closer it gets to an exterior area (GI tract, alveoli, skin), the more likely it is to encounter foreign antigens. Once the embryonic state is triggered, the cells avoid attack by constantly changing antigenic expression much as is accomplished by parasites.
Telomere Degradation is that normal process that determines the number of cell divisions that a cell will undertake in its lifetime. The Telomere of a daughter cell sheds some of its substance with every division and when it has shed most or all of its components, it triggers Apoptosis. When a daughter cell does not degrade its telomere, it becomes an immortal cell like the stem cell. Full degradation brings on apoptosis but apoptosis can occur without the full degradation of the telomere.
Displacement is the physical movement of the cell into an area where it will die from lack of resources or from an attack by pathogens. Cancer will not take place unless the cell can remain within the tissues of the organism.
Much work has been done on oncogenes (tumor promoters) and mutations in tumor suppressors as causes of cancer. These theories are not incompatible with the CRF theory. It is only after the cell loses contact and activates a different part of its genome that mutated genes begin to express themselves and perhaps contribute to a more malignant cancer state. Oncogenes are merely facilitators of the embryonic state.
One must be aware that the cause of cancer is the reactivation of the embryonic genomic program and that, I believe, begins with loss of contact. Why should loss of contact result in such changes? Mechanically, it has been shown that permeating the cell are actin fibers that span--like the spokes of a wheel--from each contact point on the cell membrane across the cell to the nucleus--the hub--and on to other contact points on the other side of the cell. When cells lose contact, these fibers probably lose tension. The loss of tension may be a simple mechanism that starts the process of genomic reprogramming by loosening the physical constraints on the nucleus.
As I've pointed out, the cell that loses contact with its neighbors will seek to re-establish contact in the only way open to it--it will start to express other CRF's that it once used in it's development from embryonic cell to adult. Because detachment is almost always necessary for the cancer state, it would seem appropriate to re-connect the cancer cell with the CRF it is seeking. These CRF's may take the form of adhesive (adherans/cadherins*) molecules but they may also be receptors looking for environmental clues. If you've seen videos of very early embryonic cell movements, you become very aware that the choreography that takes place shows very little physical contact between cells. It has been frequently demonstrated that cells react positively or negatively to chemical gradients. If we can produce these chemical attractants in quantity, we can direct metastatic cells to an area where their development can be further directed or where they can be corralled into a kind of killing zone. Also, as it is possible to put cancer cells in an embryo and have them revert to normalcy, why not put embryo or just embryonic CRF's into a cancerous mass? I envision having nano technology producing inert cell-like structures on which CRF's could be placed. These would be infused into an organism where they would attach to cancer cells in order to complete their development. Plastic beads coated with certain substances are already being used to activate neuronal repair.
I would like to re-iterate the evidence for this theory. I will limit my comments to those aspects that relate to CRF's.
The cancers that are most prevalent are those where the cells are exposed to noxious elements: bacteria in the gut, tar in the lungs, UV light on the skin, viruses in the genital areas. These elements may break or denature the CRF's. Brain cells are protected from the environment by a special barrier lacking in other tissues.
Cancers that are rare have extensive CRF's (neurons or circulating white blood cells--the latter use CRF's to tell friend from foe). When brain cancer does occur, it is the supportive cells that turn cancerous, not the neurons.
Bone cancers, where the cells are under additional physical constraints, are not as prone to cancer as epithelial cells. I believe bone is mostly a metastatic site and not a primary site but I may be wrong.
Cells undergoing high replication rates are more prone to cancer than those with lower rates. Cells that are rapidly duplicating (epithelial, blood cell progenitors) expose their CRF's to greater danger from environmental agents.
Agents that constantly break apart cells (and their connections) are known to cause cancers like mesothelioma. The pancreas produces enzymes that could conceivably attack it's own CRF's.
Cancer is a disease of older people because their cells have had more opportunity to be subjected to noxious elements like tobacco tars and UV damage that degrade the CRF's.
Ebryonic Stem Cells were recently shown to immunize mice against colon cancer. The immunity may have come about from any number of molecules that cancer cells and embryonic cells have in common and that are different from normal adult cells. I think the main antigens are the CRF's that cancer cells have in common with those of the embryo. An interesting finding was that IPSC's or artificially produced pluripotential cells did not elicit an immune response. At present, I have no explanation for this other than to say that IPSC's appear not to be the exact equivalent of embryonic stem cells; at least, with regard to the antigenic molecules expressed on their cell membranes or released extracellularly.
Many more factors play a role in the development of the various cancers but the common denominator--the grand initiator--is the loss of self-identity that occurs when a cell loses contact with its neighbors.
*It is interesting to note that adhesive molecules are kept in the lock position with calcium--take away the calcium and the molecules unlock. It is calcium that is recommended in the prevention of cancer of the GI tract.
The Cell Recognition Factor theory of cancer maintains that detachment of a cell from its neighbors is necessary for most cancers to arise. After that, a malfunction or replenishment of the telomere, or a reversion to stem cell, is necessary to permit the growth of cancer cells. The immune system then comes into play in keeping cancer cells in check or in promoting their elimination. A daughter cell has three additional hurdles to overcome on its road to cancer. It must eliminate the threat of apoptosis; eliminate telomere degradation; and, prevent itself from ending up in an inhospitable environment away from resources.
I. Stem cell (immortal)
. a. Detach from neighbors
. b. Escape from Immune Surveillance
II. Daughter cell (specialized, mortal)
. a. Detach from neighbors
. b. Escape from Immune Surveillance
. c. Prevent Apoptosis
. d. Stop Degradation of the Telomere
. e. Prevent displacement into the environment (for example, epithelial cells
sloughing off into the GI tract)
Detachment refers to the loss of cell recognition factors (CRF's). If it remains attached, it means that the cell will continue to function in its original capacity. Detachments are usually the result of environmental factors that denature the adhesive molecules on their membranes but can result from genetic or epigenetic changes that alter the correct CRF expression for that cell type. Detachment is necessary because while the cell is attached, the genome is frozen in a particular stage-specific state. It is only through detachment that the genome is free to engage in reprogramming. Unfortunately, in an adult, the reprogramming that occurs creates a cell looking for stimuli that are no longer in play (those of the embryonic environment).
Why does a cell revert to such an early time period in development? The reason is that the adult cell is the end stage of the process, and any earlier cell type is just embryonic.
At an embryonic period, most cells are migratory and malleable; capable of taking on the characteristics of whatever adult cell type was required for that area of the developing organism that they happened to be in. However, they can only do this if the other cells in the area have not yet reached the adult stage. Once the adult specification is set, no embryonic cell has the mechanism to change into that adult cell type. The options are to die as a result of apoptosis or immune surveillance.
Apoptosis is that process which results in the death of the cell when certain conditions are right. The cell undergoing apoptosis self-destructs based on its own determination or on the orders of an immune cell. Apoptosis is not seen extensively in embryonic tissue for two reasons. First, the degradation of cells could create an environment that may interfere with development. Second, embryonic cells can easily reprogram themselves according to where they happen to be. If they lose contact with their neighbors, they can reprogram instead of self-destructing. While the embryonic state is in play, the right CRF's are available. It is only when the adult state is reached that cells could end up in a limbo state whenever they lose contact with neighbors and begin to express CRF's that are no longer expressed by any of the neighboring cells. [I developed the CRF theory based on the work of a female researcher in the '60's or '70's who took cancer cells and reverted them to normal by putting them in an embryonic environment.]
Immune Surveillance Avoidance means that immune cells are not getting close enough to the cell to initiate killing functions, or that immune cells are dysfunctional. This would partly explain the high prevalence of epithelial cell cancers. Immune cells typically respond to deeper invasions that break through the barrier imposed by epithelial cells. If an immune cell were to get too close to the exterior (or the inside of the gut), it would very likely respond with an unnecessary attack for it would very likely encounter antigens that would trigger it into action. The closer it gets to an exterior area (GI tract, alveoli, skin), the more likely it is to encounter foreign antigens. Once the embryonic state is triggered, the cells avoid attack by constantly changing antigenic expression much as is accomplished by parasites.
Telomere Degradation is that normal process that determines the number of cell divisions that a cell will undertake in its lifetime. The Telomere of a daughter cell sheds some of its substance with every division and when it has shed most or all of its components, it triggers Apoptosis. When a daughter cell does not degrade its telomere, it becomes an immortal cell like the stem cell. Full degradation brings on apoptosis but apoptosis can occur without the full degradation of the telomere.
Displacement is the physical movement of the cell into an area where it will die from lack of resources or from an attack by pathogens. Cancer will not take place unless the cell can remain within the tissues of the organism.
Much work has been done on oncogenes (tumor promoters) and mutations in tumor suppressors as causes of cancer. These theories are not incompatible with the CRF theory. It is only after the cell loses contact and activates a different part of its genome that mutated genes begin to express themselves and perhaps contribute to a more malignant cancer state. Oncogenes are merely facilitators of the embryonic state.
One must be aware that the cause of cancer is the reactivation of the embryonic genomic program and that, I believe, begins with loss of contact. Why should loss of contact result in such changes? Mechanically, it has been shown that permeating the cell are actin fibers that span--like the spokes of a wheel--from each contact point on the cell membrane across the cell to the nucleus--the hub--and on to other contact points on the other side of the cell. When cells lose contact, these fibers probably lose tension. The loss of tension may be a simple mechanism that starts the process of genomic reprogramming by loosening the physical constraints on the nucleus.
As I've pointed out, the cell that loses contact with its neighbors will seek to re-establish contact in the only way open to it--it will start to express other CRF's that it once used in it's development from embryonic cell to adult. Because detachment is almost always necessary for the cancer state, it would seem appropriate to re-connect the cancer cell with the CRF it is seeking. These CRF's may take the form of adhesive (adherans/cadherins*) molecules but they may also be receptors looking for environmental clues. If you've seen videos of very early embryonic cell movements, you become very aware that the choreography that takes place shows very little physical contact between cells. It has been frequently demonstrated that cells react positively or negatively to chemical gradients. If we can produce these chemical attractants in quantity, we can direct metastatic cells to an area where their development can be further directed or where they can be corralled into a kind of killing zone. Also, as it is possible to put cancer cells in an embryo and have them revert to normalcy, why not put embryo or just embryonic CRF's into a cancerous mass? I envision having nano technology producing inert cell-like structures on which CRF's could be placed. These would be infused into an organism where they would attach to cancer cells in order to complete their development. Plastic beads coated with certain substances are already being used to activate neuronal repair.
I would like to re-iterate the evidence for this theory. I will limit my comments to those aspects that relate to CRF's.
The cancers that are most prevalent are those where the cells are exposed to noxious elements: bacteria in the gut, tar in the lungs, UV light on the skin, viruses in the genital areas. These elements may break or denature the CRF's. Brain cells are protected from the environment by a special barrier lacking in other tissues.
Cancers that are rare have extensive CRF's (neurons or circulating white blood cells--the latter use CRF's to tell friend from foe). When brain cancer does occur, it is the supportive cells that turn cancerous, not the neurons.
Bone cancers, where the cells are under additional physical constraints, are not as prone to cancer as epithelial cells. I believe bone is mostly a metastatic site and not a primary site but I may be wrong.
Cells undergoing high replication rates are more prone to cancer than those with lower rates. Cells that are rapidly duplicating (epithelial, blood cell progenitors) expose their CRF's to greater danger from environmental agents.
Agents that constantly break apart cells (and their connections) are known to cause cancers like mesothelioma. The pancreas produces enzymes that could conceivably attack it's own CRF's.
Cancer is a disease of older people because their cells have had more opportunity to be subjected to noxious elements like tobacco tars and UV damage that degrade the CRF's.
Ebryonic Stem Cells were recently shown to immunize mice against colon cancer. The immunity may have come about from any number of molecules that cancer cells and embryonic cells have in common and that are different from normal adult cells. I think the main antigens are the CRF's that cancer cells have in common with those of the embryo. An interesting finding was that IPSC's or artificially produced pluripotential cells did not elicit an immune response. At present, I have no explanation for this other than to say that IPSC's appear not to be the exact equivalent of embryonic stem cells; at least, with regard to the antigenic molecules expressed on their cell membranes or released extracellularly.
Many more factors play a role in the development of the various cancers but the common denominator--the grand initiator--is the loss of self-identity that occurs when a cell loses contact with its neighbors.
*It is interesting to note that adhesive molecules are kept in the lock position with calcium--take away the calcium and the molecules unlock. It is calcium that is recommended in the prevention of cancer of the GI tract.
Comments
I enjoyed your blog very much. I am a graduate student but I am not working on cancer, but I read a lot. I find your arguments very compelling. If you have time, could you please send me the references for these arguments so that I can learn about it more. Just links or citations are enough.
amann_deep@yahoo.co.uk
Thank you,
Deepak