Tumor reversion and embryo morphogenetic factors

Proietti, Sara; Cucina, Alessandra; Pensotti, Andrea; Fuso, Andrea; Marchese, Cinzia; Nicolini, Andrea; Bizzarri, Mariano

doi:10.1016/j.semcancer.2020.09.005

Cited by 19 publications

(13 citation statements)

References 94 publications

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“…It is evident that epigenetic rather than genetic changes in a tumor are another representation, perhaps a better one, of what constitutes cancer [10,21,22]. Epigenetics captures dynamic and interactive processes in a tumor.…”

Section: Genetics Vs Epigeneticsmentioning

confidence: 99%

Stem Cell Theory of Cancer: Origin of Tumor Heterogeneity and Plasticity

Zhang

Wood

et al. 2021

Cancers

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In many respects, heterogeneity is one of the most striking revelations and common manifestations of a stem cell origin of cancer. We observe heterogeneity in myriad mixed tumors including testicular, lung, and breast cancers. We recognize heterogeneity in diverse tumor subtypes in prostate and kidney cancers. From this perspective, we illustrate that one of the main stem-ness characteristics, i.e., the ability to differentiate into diverse and multiple lineages, is central to tumor heterogeneity. We postulate that cancer subtypes can be meaningless and useless without a proper theory about cancer’s stem cell versus genetic origin and nature. We propose a unified theory of cancer in which the same genetic abnormalities, epigenetic defects, and microenvironmental aberrations cause different effects and lead to different outcomes in a progenitor stem cell versus a mature progeny cell. We need to recognize that an all-encompassing genetic theory of cancer may be incomplete and obsolete. A stem cell theory of cancer provides greater universality, interconnectivity, and utility. Although genetic defects are pivotal, cellular context is paramount. When it concerns tumor heterogeneity, perhaps we need to revisit the conventional wisdom of precision medicine and revise our current practice of targeted therapy in cancer care.

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Section: Genetics Vs Epigeneticsmentioning

confidence: 99%

Stem Cell Theory of Cancer: Origin of Tumor Heterogeneity and Plasticity

Zhang

Wood

et al. 2021

Cancers

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“…Moreover, the components of the microenvironment can be targeted to restore lost niches or reverse niche dysfunction, thus restoring or enhancing endogenous regenerative potential. In anti-cancer therapy, tumor microenvironment can be treated with stem cells to revert malignant phenotypes (process of tumor reversion) (Proietti et al 2020).…”

Section: Regenerative Medicine Stem Cells and The Microenvironment: A...mentioning

confidence: 99%

Stem Cells and the Microenvironment: Reciprocity with Asymmetry in Regenerative Medicine

Militello

Bertolaso

2022

Acta Biotheor

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Much of the current research in regenerative medicine concentrates on stem-cell therapy that exploits the regenerative capacities of stem cells when injected into different types of human tissues. Although new therapeutic paths have been opened up by induced pluripotent cells and human mesenchymal cells, the rate of success is still low and mainly due to the difficulties of managing cell proliferation and differentiation, giving rise to non-controlled stem cell differentiation that ultimately leads to cancer. Despite being still far from becoming a reality, these studies highlight the role of physical and biological constraints (e.g., cues and morphogenetic fields) placed by tissue microenvironment on stem cell fate. This asks for a clarification of the coupling of stem cells and microenvironmental factors in regenerative medicine. We argue that extracellular matrix and stem cells have a causal reciprocal and asymmetric relationship in that the 3D organization and composition of the extracellular matrix establish a spatial, temporal, and mechanical control over the fate of stem cells, which enable them to interact and control (as well as be controlled by) the cellular components and soluble factors of microenvironment. Such an account clarifies the notions of stemness and stem cell regeneration consistently with that of microenvironment.

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“…Studies demonstrated that when tumor cells are placed within a “normal” morphogenetic milieu, they can be “reprogrammed” (thus acquiring a healthy phenotype de novo) and can then behave as native cells [ 99 ]. For example, several cancers undergo partial or complete reversion after exposure to embryonic environments [ 100 ]. This phenotypic reversion can be achieved despite the large number of genome alterations presented in cancerous cells and is related to inhibition of the migrating/invasive phenotype of cancer cells by some low-molecular-weight factors expressed by early embryonic microenvironments [ 101 , 102 , 103 , 104 ].…”

Section: Discussionmentioning

confidence: 99%

Life Entrapped in a Network of Atavistic Attractors: How to Find a Rescue

Kasperski

2022

IJMS

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In view of unified cell bioenergetics, cell bioenergetic problems related to cell overenergization can cause excessive disturbances in current cell fate and, as a result, lead to a change of cell-fate. At the onset of the problem, cell overenergization of multicellular organisms (especially overenergization of mitochondria) is solved inter alia by activation and then stimulation of the reversible Crabtree effect by cells. Unfortunately, this apparently good solution can also lead to a much bigger problem when, despite the activation of the Crabtree effect, cell overenergization persists for a long time. In such a case, cancer transformation, along with the Warburg effect, may occur to further reduce or stop the charging of mitochondria by high-energy molecules. Understanding the phenomena of cancer transformation and cancer development has become a real challenge for humanity. To date, many models have been developed to understand cancer-related mechanisms. Nowadays, combining all these models into one coherent universal model of cancer transformation and development can be considered a new challenge. In this light, the aim of this article is to present such a potentially universal model supported by a proposed new model of cellular functionality evolution. The methods of fighting cancer resulting from unified cell bioenergetics and the two presented models are also considered.

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Tumor reversion and embryo morphogenetic factors

Cited by 19 publications

References 94 publications

Stem Cell Theory of Cancer: Origin of Tumor Heterogeneity and Plasticity

Stem Cell Theory of Cancer: Origin of Tumor Heterogeneity and Plasticity

Stem Cells and the Microenvironment: Reciprocity with Asymmetry in Regenerative Medicine

Life Entrapped in a Network of Atavistic Attractors: How to Find a Rescue

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