Process analysis of carcinogenesis: concept derivation of the tissue function "preservation of a homogeneous gene expression"

Our plain-English summary of Process analysis of carcinogenesis: concept derivation of the tissue function "preservation of a homogeneous gene expression", by T. Löser (Theory in Biosciences = Theorie in Den Biowissenschaften, 2018).

The study

• Author: T. Löser
• Journal: Theory in Biosciences = Theorie in Den Biowissenschaften
• Published: 2018;137(1):85-97
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

A new system for maintaining homogeneous gene expression in tissue and for destroying through apoptosis nonconforming cells is introduced. This functionality is called the "similarity comparison." Accordingly, the survival of mutated cells is hindered due to reduced gene expression. That, in turn, maintains the homogeneity of the tissue and prevents tumors from developing. The concept of the similarity comparison is that every stationary cell in every tissue constantly screens the gene expression of its neighbors. Cells process the signals, and when the difference between neighbors exceeds some threshold, a signal is triggered. An under-expressing cell then either increases its gene expression or apoptosis occurs. The oversight role of the similarity comparison can, under certain conditions, be disrupted, such that mutated cells in the tissue can survive. This is possible only when surrounding normal cells exhibit reduced gene expression. In this case, the normal cells and mutated cells have similar gene expression, and the signal for apoptosis is not triggered. The mutated cells survive, and a tumor can develop. The importance of the similarity comparison as an oversight mechanism is studied. Examples are considered.

In plain English

This theoretical short communication did not study patients or workers. Using a thermodynamics-based view, the author proposed a "similarity comparison," in which cells check their neighbors' gene expression and cells that differ too much die by apoptosis (programmed cell death). The author argued that this check can fail when surrounding normal cells have reduced gene expression, as in chronic inflammation. A mutated cell may then differ from its neighbors by less than a tolerance threshold, so it can survive and a tumor can develop. In this model, highly mutated cells still die. Citing other publications, the author described asbestos as inert and non-mutagenic but able to cause chronic inflammation. The author reported 902 new mesothelioma cases recognized as occupational illness in Germany in 2011. Alongside a figure of more than 560,000 people registered for occupational preventive healthcare, the author gave a crude rate of 0.16% in the highest risk group. The author stated that actual incidence among workers exposed for 25 years or more is not known. The author concluded that chronic inflammation with hyperplasia or metaplasia appears to be the main pathway but is not sufficient alone.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Theoretical short communication. The author derives a proposed concept (the 'similarity comparison') from existing knowledge using a thermodynamics-inspired view. It is illustrated with case examples drawn from published literature and German cancer statistics. No new data were collected.
• Who was studied: No study population. The paper discusses illustrative examples. Cigarette smoke, asbestos and radioactivity (Hiroshima) are the outside carcinogens. Breast and prostate cancer are the examples with internal causes. Most figures are German and come from other sources.
• Exposure: Asbestos in general; no fiber type is named. Citing other publications, the author describes asbestos as inert and non-mutagenic but able to cause chronic inflammation through mechanical irritation. Smoking, radiation and hormone-related tissue changes are also discussed.
• Main results:
  • The author proposed that tissue keeps gene expression uniform through signals between neighboring cells. Cells that still deviate are removed by apoptosis.
  • The author proposed that this 'tissue surveillance' switches off only when the difference in gene expression between normal and mutated cells falls below a tolerance threshold. Reduced gene expression in the normal cells is how such a state is reached, and mutated cells can then survive.
  • In the proposed model, cells with a high degree of mutation still undergo apoptosis, in normal tissue and in previously damaged tissue alike.
  • Asbestos example, figure taken from other sources: in Germany, more than 560,000 people were registered in 2011 for occupational preventive healthcare under the German workers' compensation insurance.
  • Asbestos example, figure taken from another publication (Neumann et al. 2013): 902 new cases of mesothelioma were recognized as occupational illness in Germany in 2011.
  • The author's own rough calculation gave a crude rate of 0.16% in the 'highest risk group'. The article does not name the denominator explicitly. The figure is consistent with 902 cases divided by the more than 560,000 registered people, not all exposed workers. It is not a measured incidence.
  • From the case examples, the author generalized that for asbestos and ionizing radiation, the latency time between last exposure and tumor diagnosis is relatively long, at one or more decades.
  • The author generalized that in the three outside-carcinogen examples (smoking, asbestos, radiation), the tumor develops on the basis of inflammatory tissue changes.
• The authors' conclusion: The author concluded that gene expression in tissue can be reduced in various ways, and that chronic inflammation with hyperplasia or metaplasia appears to be the main pathway. The author added that this alone is not sufficient and that other factors must also be involved.
• Limitations the authors state:
  • The author described the similarity comparison as a basic model that needs further development.
  • The author noted that some cell types in real tissues and stroma are essential to the tissue but are not covered by the similarity comparison.
  • For the asbestos example, the author noted that the actual incidence among workers exposed to asbestos for 25 years or more is not known. It could be greater than the crude rate given.

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Apoptosis.

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