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Correct Identification of Cell of Origin May Explain Many Aspects of Cancer: The Role of Neuroendocrine Cells as Exemplified from the Stomach

1
Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7006 Trondheim, Norway
2
Department of Pathology, St. Olav’s Hospital, Trondheim University Hospital, 7006 Trondheim, Norway
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(16), 5751; https://doi.org/10.3390/ijms21165751
Received: 3 July 2020 / Revised: 5 August 2020 / Accepted: 5 August 2020 / Published: 11 August 2020
(This article belongs to the Special Issue Gastric Cancers: Molecular Pathways and Candidate Biomarkers 3.0)
Cancers are believed to originate from stem cells. Previously, the hypothesis was that tumors developed due to dedifferentiation of mature cells. We studied the regulation of gastric acid secretion and showed that gastrin through the gastrin receptor stimulates enterochromaffin-like (ECL) cell histamine release and proliferation. In animal and human studies, we and others showed that long-term hypergastrinemia results in ECL cell-derived tumor through a sequence of hyperplasia, dysplasia, neuroendocrine tumors (NETs), and possibly neuroendocrine carcinomas (NECs) and adenocarcinomas of diffuse type. Perhaps, other cancers may also have their origin in differentiated cells. Knowledge of the growth regulation of the cell of origin is important in cancer prophylaxis and treatment. Physiology plays a central role in carcinogenesis through hormones and other growth factors. Every cell division implies a small risk of mutation; thus mitogens are also mutagens. Moreover, metastasis of slow proliferating cells may also explain so-called tumor dormancy and late recurrence. View Full-Text
Keywords: carcinogenesis; cell of origin; dormancy; ECL cell; gastrin; gastric cancer; hormones carcinogenesis; cell of origin; dormancy; ECL cell; gastrin; gastric cancer; hormones
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Waldum, H.; Mjønes, P.G. Correct Identification of Cell of Origin May Explain Many Aspects of Cancer: The Role of Neuroendocrine Cells as Exemplified from the Stomach. Int. J. Mol. Sci. 2020, 21, 5751.

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