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Updated: Aug 5, 2025
Establishment and Characterization of Small Bowel Neuroendocrine Tumor Spheroids
Published on: October 14, 2019
Somatostatin receptor 2 in 10 different types of human non-neoplastic gastrointestinal neuroendocrine cells
Hirofumi Watanabe1, Fumiyoshi Fujishima1, Michiaki Unno2
1Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan.
Abstract:
Somatostatin is known to inhibit the secretion of various hormones by acting on endocrine cells through the somatostatin receptor 2 (SSTR2). Immunohistochemical evaluation of SSTR2 has become increasingly important in clinical practice to determine treatment strategies for patients with a neuroendocrine tumor (NET). Gastrointestinal (GI) tracts contain various neuroendocrine cells that constitute a diffuse endocrine system and some NETs are derived from those cells. In addition, NETs have been well known to express a variable spectrum of proteins shared by their normal cell counterparts of the specific anatomical sites. Thus, we may derive the kinetics of SSTR2 expression of NETs, including de novo expression, from the SSTR2 expression of the corresponding normal neuroendocrine cells. Therefore, a detailed study on the distribution of SSTR2 in normal human neuroendocrine cells may contribute to understanding the expression of SSTR2 in GI-NETs. However, the detailed cellular localization of SSTR2 in non-neoplastic neuroendocrine cells remains unknown. Therefore, we immunolocalized SSTR2 in neuroendocrine cells of normal human GI tracts, including the stomach, duodenum, ileum, and rectum, obtained from 41 surgically resected tissue specimens. Double immunohistochemistry of SSTR2 and hormones or hormone-associated proteins was performed. In all GI neuroendocrine cells, cell types other than D- and EC-cells demonstrated a high percentage of SSTR2-positive cases or a high double-positive ratio. In particular, EC-cells showed lower SSTR2-positive ratios in all sites. Midgut NETs, which often produce serotonin, are excellent targets for somatostatin analogs and are positive for SSTR2. Thus, we speculated that EC-cell NETs might lead to the de novo expression of SSTR2. In addition, a previous report showed high SSTR2 expression in ECL-cell NETs and gastrinomas, which could be because they are derived from neuroendocrine cells with high SSTR2 expression. This study may contribute to understanding the expression of SSTR2 in GI-NETs.
Insights
Somatostatin receptor 2 (SSTR2) expression varies in normal gastrointestinal neuroendocrine cells, with EC-cells showing lower SSTR2 positivity. This impacts understanding neuroendocrine tumor (NET) SSTR2 expression and treatment strategies.
Area of Science:
- Endocrinology
- Gastroenterology
- Oncology
Background:
- Somatostatin inhibits hormone secretion via somatostatin receptor 2 (SSTR2).
- SSTR2 evaluation is crucial for neuroendocrine tumor (NET) treatment.
- Understanding SSTR2 in normal neuroendocrine cells aids GI-NET research.
Purpose of the Study:
- To investigate the cellular localization of SSTR2 in normal human gastrointestinal (GI) neuroendocrine cells.
- To correlate SSTR2 expression in normal GI neuroendocrine cells with SSTR2 expression in GI-NETs.
Main Methods:
- Immunohistochemistry was used to localize SSTR2 in neuroendocrine cells of the stomach, duodenum, ileum, and rectum.
- Double immunohistochemistry was performed for SSTR2 and hormone markers.
- Analysis included 41 surgically resected normal human GI tissue specimens.
Main Results:
- Most GI neuroendocrine cell types, excluding D- and EC-cells, showed high SSTR2 positivity.
- Enterochromaffin (EC)-cells exhibited lower SSTR2-positive ratios across all GI sites.
- Midgut NETs, often SSTR2-positive, may involve de novo SSTR2 expression in EC-cell NETs.
Conclusions:
- Normal GI neuroendocrine cell SSTR2 distribution provides insights into GI-NET SSTR2 expression patterns.
- Lower SSTR2 expression in normal EC-cells suggests potential de novo SSTR2 expression in EC-cell NETs.
- This study contributes to understanding SSTR2 heterogeneity in GI-NETs and informs treatment strategies.
