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

Mjønes, Patricia

doi:10.3390/ijms21165751

Cited by 7 publications

(7 citation statements)

References 76 publications

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“…Another possibility may be that the cell of origin due to inherent qualities like low expression of factors contributing to cell adhesion may cause metastasis spread at an early phase of malignant development when the proliferation still is rather low. Such a phenomenon may explain the so-called dormancy [47]. As we see it, the possibility that some cancer cells go to sleep and awake after many years does not seem very plausible, although until now it has been the prevailing theory [45].…”

Section: Clinical Aspects Of Ccrccmentioning

confidence: 88%

Clear Cell Renal Cancer, a Tumour with Neuroendocrine Features Originating from the Erythropoietin-Producing Cell

Waldum¹,

Mjønes²

2023

Renal Cell Carcinoma - Recent Advances, New Perspectives and Applications

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The dominating type of kidney cancer is the clear cell renal cell cancer (ccRCC), hitherto been thought to develop from proximal tubule cells. However, the ability of tubule cells to proliferate is at best controversial. ccRCCs show many peculiarities like erythrocytosis due to erythropoietin overproduction and a combination of early metastases and sometimes apparent dormancy and late recurrence, features in common with neuroendocrine tumours (NETs). We have shown that most ccRCCs express erythropoietin and the neuroendocrine marker neuron-specific enolase, and other neuroendocrine markers in a percentage of the cancers. Missense mutation in von Hippel–Lindau (VHL) factor is rather specific for ccRCC found in familial and sporadic forms. The function of VHL factor is together with other proteins to destroy hypoxia-inducible factors (HIFs), central in adaptation to hypoxia. Lack of functioning VHL factor results in continuous overstimulation of the erythropoietin-producing cell to release erythropoietin and parallelly to proliferate, and in long-term mutations and malignant transformation. Thus, ccRCC occurs about 30 years later in sporadic cases compared with familial von Hippel–Lindau syndrome, reflecting the time necessary for two versus one genetic change. Embryologically, there are many arguments favouring neural crest origin of the erythropoietin-producing cell.

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Section: Clinical Aspects Of Ccrccmentioning

confidence: 88%

Clear Cell Renal Cancer, a Tumour with Neuroendocrine Features Originating from the Erythropoietin-Producing Cell

Waldum¹,

Mjønes²

2023

Renal Cell Carcinoma - Recent Advances, New Perspectives and Applications

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“…The origin of GNEC and MiNEN has not been determined. One view is that during the proliferation of normal enterochromaffin-like cells, superimposed gene mutations result in gastric neuroendocrine tumor formation, which further progresses to GNEC, diffuse gastric adenocarcinoma and finally signet ring cell carcinoma[ 10 - 12 ]. Another view is that gastric neuroendocrine cells predominantly arise from neuroendocrine precursor cell clones occurring in preceding adenocarcinoma components, which transform into neuroendocrine cells during rapid clonal expansion.…”

Section: Discussionmentioning

confidence: 99%

Mixed large and small cell neuroendocrine carcinoma of the stomach: A case report and review of literature

Li¹,

Lu²,

Chen³

et al. 2022

WJCC

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BACKGROUND Gastric neuroendocrine carcinoma (GNEC) is a rare histological subtype of gastric cancer, which is categorized into small cell and large cell neuroendocrine carcinomas. It is characterized by strong invasiveness and poor prognosis. Mixed large and small cell neuroendocrine carcinoma (L/SCNEC) is an extremely rare pathological type of gastric cancer, and there have been no reports on this situation until now. CASE SUMMARY Herein, we first present a 57-year-old patient diagnosed with L/SCNEC of the stomach. A 57-year-old Chinese male presented with epigastric discomfort. Outpatient gastroscopic biopsy was performed, and pathological examination revealed that the cardia was invaded by adenocarcinoma. The patient underwent laparoscopic-assisted radical proximal subtotal gastrectomy and was diagnosed with L/SCNEC. He refused adjuvant treatment and was followed up every 3 mo. Eight months after the operation, the patient showed no evidence of local recurrence or distant metastasis. CONCLUSION We advocate conducting further genomic studies to explore the origin of gastric large cell and small cell neuroendocrine carcinoma and using different chemotherapy schemes according to large or small cell neuroendocrine carcinoma of the stomach for clinical research to clarify the heterogeneity of GNEC and improve the prognosis of patients with GNEC.

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“…We are pleased that we no longer are alone with the present views, since a Chinese group, one year ago in a review, seemed to share most of them [ 138 ]. We will also add that metastases of slow-proliferating cancer cells, such as neuroendocrine cells, may explain the apparent dormancy of cancer cells giving rise to very late cancer recurrence [ 139 ]. The central role of the ECL cell in gastric physiology and pathology [ 140 ] is depicted in Figure 1 .…”

Section: Discussionmentioning

confidence: 99%

“…Figure1. The central role of gastrin and the enterochromaffin-like (ECL) cell in the regulation of gastric acid secretion and in gastric carcinogenesis (reproduced by permission from the publisher, reference[139]). …”

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confidence: 99%

Towards Understanding of Gastric Cancer Based upon Physiological Role of Gastrin and ECL Cells

Mjønes

2020

Cancers

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The stomach is an ideal organ to study because the gastric juice kills most of the swallowed microbes and, thus, creates rather similar milieu among individuals. Combined with a rather easy access to gastric juice, gastric physiology was among the first areas to be studied. During the last century, a rather complete understanding of the regulation of gastric acidity was obtained, establishing the central role of gastrin and the histamine producing enterochromaffin-like (ECL) cell. Similarly, the close connection between regulation of function and proliferation became evident, and, furthermore, that chronic overstimulation of a cell with the ability to proliferate, results in tumour formation. The ECL cell has long been acknowledged to give rise to neuroendocrine tumours (NETs), but not to play any role in carcinogenesis of gastric adenocarcinomas. However, when examining human gastric adenocarcinomas with the best methods presently available (immunohistochemistry with increased sensitivity and in-situ hybridization), it became clear that many of these cancers expressed neuroendocrine markers, suggesting that some of these tumours were of neuroendocrine, and more specifically, ECL cell origin. Thus, the ECL cell and its main regulator, gastrin, are central in human gastric carcinogenesis, which make new possibilities in prevention, prophylaxis, and treatment of this cancer.

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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

Cited by 7 publications

References 76 publications

Clear Cell Renal Cancer, a Tumour with Neuroendocrine Features Originating from the Erythropoietin-Producing Cell

Clear Cell Renal Cancer, a Tumour with Neuroendocrine Features Originating from the Erythropoietin-Producing Cell

Mixed large and small cell neuroendocrine carcinoma of the stomach: A case report and review of literature

Towards Understanding of Gastric Cancer Based upon Physiological Role of Gastrin and ECL Cells

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