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

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

The Enterochromaffin-like [ECL] Cell—Central in Gastric Physiology and Pathology

Background: Studies on the regulation of gastric and pancreatic secretion began more than 100 years ago. Secretin was the first hormone postulated to exist, initiating the field of endocrinology. Gastrin produced in the antral mucosa was the second postulated hormone, and together with histamine and acetylcholine, represent the three major gastric acid secretagogues known since 1920. For a long time, the mast cell was the only recognized histamine-producing cell in the oxyntic mucosa and, in the mid-1980s, the ECL cell was recognized as the cell producing histamine, taking part in the regulation of gastric acid secretion. Methods: This review is based upon literature research and personal knowledge. Results: The ECL cell carries the gastrin receptor, and gastrin regulates its function (histamine release) as well as proliferation. Long-term hypergastrinemia results in gastric neoplasia of variable malignancies, implying that gastric hypoacidity resulting in increased gastrin release will induce gastric neoplasia, including gastric cancer. Conclusions: The trophic effect of gastrin on the ECL cell has implications to the treatment with inhibitors of acid secretion

DS_10.1369_0022155418792032 – Supplemental material for Characterization of FGD5 Expression in Primary Breast Cancers and Lymph Node Metastases

<p>Supplemental material, DS_10.1369_0022155418792032 for Characterization of FGD5 Expression in Primary Breast Cancers and Lymph Node Metastases by Marit Valla, Patricia G. Mjønes, Monica J. Engstrøm, Borgny Ytterhus, Diana L. Bordin, Barbara van Loon, Lars A. Akslen, Lars J. Vatten, Signe Opdahl and Anna M. Bofin in Journal of Histochemistry & Cytochemistry</p