Pathogenesis of cancer - Сергей Алексеевич Шалин
Important and undeniable statements:
— malignant cells are more similar to each other than normal cells are to each other;
— malignant cells have fewer differences between themselves than the differences between malignant cells and normal cells;
— not a single property that malignant cells possess is possessed by epithelial cells, and not a single function of the epithelium (integumentary, protective, exocrine) is transferred to malignant cells;
— the basic principles of the “birth” of a malignant cell, the growth of the primary focus and the development of the malignant process of various organs and tissues are completely identical.
The question of which cell can lay claim to the role of the progenitor cell of the primary malignant stem cell of solid tumors remains controversial. When analyzing all the cells of the human body, only Mononuclear cells (Monocytes) can claim this role, and there is every reason for this statement, they are:
1. They are somatic proliferating cells.
2. They have a long life cycle (months).
3. They have sufficient autonomy: they are able to move freely throughout the host body through the blood stream, penetrate and migrate in various organs and tissues.
4. They are an intermediate development option in the red bone marrow and bloodstream, and in tissues they are transformed into tissue macrophages.
5. In anaerobic conditions, they can independently switch to the anaerobic type of energy production.
6. They can take on the phenotype of microenvironmental cells — mesenchymal-epithelial transition.
7. They have the ability to influence various vital processes: hematopoiesis, homeostasis, immunity, proliferation, maturation and differentiation of cells, etc. Thus, a mononuclear cell (Monocyte) is a cell that can lay claim to the role of a precursor cell of the primary malignant stem cell of solid tumors.
STEPS
The stages of formation and successive change of generations of malignant stem cells during mononuclear oncogenesis correspond to the stages of formation and successive change of generations of stem cells during embryonic hematopoiesis. The presented comparative analysis of the stages of formation and sequential change of generations of stem cells during embryonic hematopoiesis and Mononuclear oncogenesis shows that Mononuclear oncogenesis is a pathological form of embryonic hematopoiesis in the postnatal period of human development.
Comparative analysis of the stages of formation and change of generations of stem cells during embryonic hematopoiesis and mononuclear oncogenesis.
— The first phase — Mesoblastic, the first generation of stem cells — in the wall of the yolk sac of the embryo, the “birth” of blood stem cells occurs — the first generation.
— The first generation of stem cells — Cytoblastic — in an isolated microcavity formed like the yolk sac of an embryo, the “germination” of a malignant stem cell occurs. Due to proliferation, mass accumulation occurs and the first generation of malignant stem cells is formed. Second phase.
— The second phase — Hepatolienal, second generation of stem cells — blood stem cells emerge from the yolk sac and populate the liver, which becomes the main organ of embryonic hematopoiesis. The second generation of blood stem cells is formed in it. Liver blood stem cells then colonize the thymus, spleen and lymph nodes.
— The second generation of stem cells Primary-focal — the malignant stem cells exit beyond the isolated micro cavity into the intercellular space and colonize it. Due to proliferation, appositional and invasive growth they organise a primary focus, where the second generation of the malignant stem cells is formed.
— The third phase Medullar (marrow) — the blood stem cells colonize the red bone marrow, where their third generation is formed — this is the final phase of the embryonic haematopoiesis. Medullar (marrow) — the blood stem cells colonize the red bone marrow, where their third generation is formed — this is the final phase of the embryonic haematopoiesis.
— The third and subsequent generations of stem cells Secondary-focal or metastatic — due to the invasive growth and angioneogenesis the malignant stem cells penetrate into the bloodstream and colonize the lymph nodes, the bone marrow, liver, lungs etc., followed by organisation of the secondary malignant focus — mature metastasis, where the third generation of the malignant stem cells is formed. Later, subsequent generations of the malignant stem cells may form.
PROTOTYPES
Mononuclear oncogenesis uses known processes and structural organizations as prototypes, according to the principle “all this was already in the body, only at a different time, in a different place and with other cellular and non-cellular elements.” The prototype of the “pretumor” bed, presented as an isolated microcavity, is the structural organization and functioning of the yolk sac of the embryo. In this case, conditions close to embryonic ones arise inside the microcavity, and the “nascent” malignant stem cell conditionally repeats the beginning of embryonic hematopoiesis. The prototype of the structural organization and functioning of the primary malignant focus is the structural organization and functioning of the red bone marrow. In this case, the primary malignant focus is presented as an independent structural unit containing all the classical characteristics of the tissue, possessing autonomy of reproduction and the ability to spread in the host organism. A prototype of the relationships between the structural elements that make up the malignant process and the relationships At the same time,
