Comment: This is an excellent article written by Gaetana Tonti, bioscience researcher and META-Health Master Practitioner about proposing a new model of who and how metastasis develop.   

Metastasis derives from the Greek META: beyond, and STASIS: to place, and is used to describe the spread of cancer cells from the primary site to another organ/part of the body. To do this, cancer cells from the first site need to move and invade the secondary site. There has been some debate about the existence of cancerous cells circulating in peripheral blood, especially in the META-medicine world; so it might be interesting to briefly report the most recent discoveries and hypotheses, and discuss META-stases from a META-perspective.

The first point is that cancer cells do exist out of the primary cancer, even though they are very rare. They are defined either as disseminated tumor cells (DTCs), which are cells deriving from the primary tumor found in bone marrow, or as circulating tumor cells (CTCs), which means found circulating in the peripheral blood. CTCs  and DTCs have been found in many different carcinoma patients and are not present in healthy subjects or patients with benign diseases.

Even though the development of disseminated metastatic diseases has been traditionally viewed as a sequential rather than concurrent process, (i.e. the disease initially occurs at the primary site, followed by local growth with dissemination to distant sites much later in time (1)), emerging data is challenging this theory (2, 3), suggesting that the presence of CTCs and DTCs is a very early, if not concomitant phenomenon, to the onset of the primary tumor.

Bone marrow has revealed to be a common homing organ for metastatic cells, independent of the primary tumor site and the pattern of overt metastases (4). This suggests a causal link  and a specific meaning for the presence of DTCs in the bone marrow.  In fact, DTCs in bone marrow have been detected in all solid tumor types suggesting that the bone marrow might be a preferred reservoir for blood-borne DTCs.

However, up to now it is unknown which environmental and internal factors can promote the recirculation of DTCs from the bone marrow niche into other distant organs – such as liver or lungs, which are common sites of metastatic spread. These tumor cells detached from the primary tumor flow in the peripheral blood and reach the bone marrow in a dormant state until internal and/or external signals enable them to move and grow out to overt metastases at different organs (5-7).

Little is known about these dormant cells and the conditions required—environmental factors (e.g., immune system, dietary changes…..stress, emotional traumas….. repair of damaged tissues in a regeneration phase)—for their ‘‘awakening’’ from the dormant phase into the dynamic phase of metastasis formation. According to conventional science the dormant state might be disturbed by both changes within the DTCs (e.g., additional DNA mutations) and the surrounding microenvironment (e.g., decrease in immune surveillance or increased angiogenetic potential (8, 9).

But what if a more bio-logical and meaningful reason existed for the explanation of this phenomenon?

Messages from the environment

Cancer cell behaviors are not regulated by a linear series of commands, but rather by networks of molecular interactions that involve positive and negative reinforcement. Switching between different cell fates that are critical for cancer (e.g., growth, differentiation, increased motility) can be triggered in normal and transformed cells, by changes in extracellular matrix (ECM) structure and cell shape distortion (10-14), ‘non-specific’ chemical solvents and electrical ion flows (15-17) that influence multiple gene activities, as well as by distinct molecular factors or specific gene mutations.

There are many studies in experimental systems suggesting that cancers can be induced to become quiescent, differentiate, die or form completely normal tissues, if provided with the correct set of complex signals, as conveyed by embryonic tissues or other microenvironmental cues  (18). This means that for some reason the environment surrounding the primary tumor becomes ‘‘activated,’’ and it can release cancer and metastasis-inducing signals.

This scenario represents a clear example of the acquisition of highly malignant cell biological traits through an adaptive mechanism, arguing strongly for adaptation/response as the prime driving force that underlies the acquisition of highly malignant traits by neoplastic cells.

A new META-perspective on cancer and META-stases

On these bases a very challenging hypothesis has been proposed:

  • Cancer as a natural wound healing related process where the outcome of the cancer mechanism is either healing the wound or exhausting the whole system (death).

The wound signaling molecules present in a tissue cause over-expression of the existing cancer-related genes, leading to the changes of certain chromosomes and cancer cell traits (19). Therefore, a  (wound–oncogene–wound healing (WOWH)) can be logically speculated: cancer formation is a natural process that organisms have used in wound healing. Briefly, when defined wounds occur in mammals, the body starts the complicated wound healing process.

Molecules such as growth factors, cytokines, and other proteins from the cells in the wound area interrupt the balance of normal molecular metabolism, leading to the activation of corresponding cancer-related genes and inducing cancerization in some cells. The cells with activated genes can secrete molecules to recruit other cells, stimulate cell proliferation, and enhance cell differentiation to repair the wound. Mostly, the wound is healed after above efforts.

However, if the wound conditions are still persistent this WOWH mechanism will not stop and more cancer cells (over-activation of the canre-related genes transformed normal cells into malignant cells (21, 21) are divided to secrete more molecules for wound healing, forming a clinical cancer mass. After the wound is healed, the molecules of a healed environment initiate cancer cell differentiation or death.

This model leads also to a new concept of metastasis.

Based on the idea that cancer cells are present to repair a wound, a META explanation of metastasis is that cancer cells in the primary tumor site can “sense” the presence of wounds at distant sites and these cancer cells can migrate through the circulation in order to heal the secondary wound. At this point it might be interesting to define the term “wound”: is it only a physical wound?! But from a META-perspective we know that there is never a physical wound without an emotional/spiritual wound. In this respect it might be interesting to point out which are the most common sites of metastasis. The most common sites for secondary tumors are the lungs, followed by the bones (with the vertebrae showing the highest frequency) and liver. The higher occurency of metastases and secondary tumors in these sites can be easily explained from a META-point. When a patient hears from a doctor that he/she has a cancer, the person can often experience death fright, as the idea of having cancer is still linked with a negative, life threatening belief. In this case the person can experience a diagnostic shock, leading to a proliferation of the lung cells in order to have an increased breathing. The explanation from the META-Medicine point of view is that during the stress phase in a conflict related death fright there is proliferation of the lung cells in order to improve breathing and survival. Similarly some people may experience a survival-existence conflict, worrying if they will survive. In this case the liver will be involved. Again, in the stress phase it will have an increase in cell activity/number, leading to a proliferation of the adeno-cells of the liver. When diagnosed with primary cancer, many people can also feel worthless, incapable, not able to sustain the situation, and in this case the bone tissue will react. As discussed previously, metastatic cells invade the bone marrow and reside in a dormant state. When triggered they cause bone tumor and following the resolution there will be calcification of cells and the bone will be stronger than before (for bones the bio-logical meaning is in the cell increase and strengthening of the bone at the end of the regeneration phase).

The final question could be “Why the cancer cells from the primary tumor migrate to the bone marrow and remain in a dormant state, waiting to be awakened and eventually migrate to secondary sites?” According to the WOWH theory these primary cancer cells might sense an emotional wound/stress, and from a META-perspective it would be a deep wound, that hits the core of who we are, the sense that lives gives to us or that we give to life… the inmost, the essential part of who we are… the marrow. I view this event as if when a person develops a primary cancer, our bodily intelligence wants to protect us, sending these primary cells directly to our core, our marrow; these cells remain there, dormant, ready to move to other organs when needed. Our body is a highly intelligent organism where every event/symptoms has a meaningful reason to exist.

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