Exposure to nonanoic acid alters small intestinal neuroendocrine tumor phenotype
Abstract Background Small intestinal neuroendocrine tumors (SI-NET) are highly differentiated and genetically stable malignant tumors, yet they often present with advanced metastatic spread at the time of diagnosis. In contrast to many other types of malignant tumors, primary SI-NET are often asympt...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-03-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-023-10722-8 |
| _version_ | 1827979472568057856 |
|---|---|
| author | Bilal Almobarak Vishal Amlani Linda Inge Tobias Hofving Andreas Muth Ola Nilsson Martin Johansson Yvonne Arvidsson Erik Elias |
| author_facet | Bilal Almobarak Vishal Amlani Linda Inge Tobias Hofving Andreas Muth Ola Nilsson Martin Johansson Yvonne Arvidsson Erik Elias |
| author_sort | Bilal Almobarak |
| collection | DOAJ |
| description | Abstract Background Small intestinal neuroendocrine tumors (SI-NET) are highly differentiated and genetically stable malignant tumors, yet they often present with advanced metastatic spread at the time of diagnosis. In contrast to many other types of malignant tumors, primary SI-NET are often asymptomatic and typically smaller in size compared to adjacent lymph node metastases. This study explores the hypothesis that stimulating the chemosensing olfactory receptor 51E1 (OR51E1) decreases SI-NET proliferation suggesting a mechanism that explains a difference in proliferative rate based on tumor location. Methods Clinical data was used to address difference in tumor size depending on location. A SI-NET tissue microarray was used to evaluate expression of OR51E1 and olfactory marker protein (OMP). Primary cultured tumor cells from 5 patients were utilized to determine the effect of OR51E1 agonist nonanoic acid on metabolic activity. The SI-NET cell line GOT1 was used to determine effects of nonanoic acid on the transcriptome as well as long-term effects of nonanoic acid exposure with regards to cell proliferation, serotonin secretion, alterations of the cell-cycle and morphology. Results Tumor size differed significantly based on location. OR51E1 and OMP were generally expressed in SI-NET. Primary SI-NET cells responded to nonanoic acid with a dose dependent altered metabolic activity and this was replicated in the GOT1 cell line but not in the MCF10A control cell line. Nonanoic acid treatment in GOT1 cells upregulated transcripts related to neuroendocrine differentiation and hormone secretion. Long-term nonanoic acid treatment of GOT1 cells decreased proliferation, induced senescence, and altered cell morphology. Conclusion Our results raise the possibility that exposure of intraluminal metabolites could represent a mechanism determining aspects of the SI-NET tumor phenotype. However, we could not causally link the observed effects of nonanoic acid exposure to the OR51E1 receptor. |
| first_indexed | 2024-04-09T21:38:25Z |
| format | Article |
| id | doaj.art-d055bd62c17549389cf2301a57fd0067 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-09T21:38:25Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-d055bd62c17549389cf2301a57fd00672023-03-26T11:12:43ZengBMCBMC Cancer1471-24072023-03-0123111210.1186/s12885-023-10722-8Exposure to nonanoic acid alters small intestinal neuroendocrine tumor phenotypeBilal Almobarak0Vishal Amlani1Linda Inge2Tobias Hofving3Andreas Muth4Ola Nilsson5Martin Johansson6Yvonne Arvidsson7Erik Elias8Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of GothenburgDepartment of Vascular Surgery, Sahlgrenska University HospitalSahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of GothenburgSahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of GothenburgDepartment of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of GothenburgSahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of GothenburgSahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of GothenburgSahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of GothenburgSahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of GothenburgAbstract Background Small intestinal neuroendocrine tumors (SI-NET) are highly differentiated and genetically stable malignant tumors, yet they often present with advanced metastatic spread at the time of diagnosis. In contrast to many other types of malignant tumors, primary SI-NET are often asymptomatic and typically smaller in size compared to adjacent lymph node metastases. This study explores the hypothesis that stimulating the chemosensing olfactory receptor 51E1 (OR51E1) decreases SI-NET proliferation suggesting a mechanism that explains a difference in proliferative rate based on tumor location. Methods Clinical data was used to address difference in tumor size depending on location. A SI-NET tissue microarray was used to evaluate expression of OR51E1 and olfactory marker protein (OMP). Primary cultured tumor cells from 5 patients were utilized to determine the effect of OR51E1 agonist nonanoic acid on metabolic activity. The SI-NET cell line GOT1 was used to determine effects of nonanoic acid on the transcriptome as well as long-term effects of nonanoic acid exposure with regards to cell proliferation, serotonin secretion, alterations of the cell-cycle and morphology. Results Tumor size differed significantly based on location. OR51E1 and OMP were generally expressed in SI-NET. Primary SI-NET cells responded to nonanoic acid with a dose dependent altered metabolic activity and this was replicated in the GOT1 cell line but not in the MCF10A control cell line. Nonanoic acid treatment in GOT1 cells upregulated transcripts related to neuroendocrine differentiation and hormone secretion. Long-term nonanoic acid treatment of GOT1 cells decreased proliferation, induced senescence, and altered cell morphology. Conclusion Our results raise the possibility that exposure of intraluminal metabolites could represent a mechanism determining aspects of the SI-NET tumor phenotype. However, we could not causally link the observed effects of nonanoic acid exposure to the OR51E1 receptor.https://doi.org/10.1186/s12885-023-10722-8NeuroendocrineSI-NETSINETSBNETNeuroendocrineSmall intestine |
| spellingShingle | Bilal Almobarak Vishal Amlani Linda Inge Tobias Hofving Andreas Muth Ola Nilsson Martin Johansson Yvonne Arvidsson Erik Elias Exposure to nonanoic acid alters small intestinal neuroendocrine tumor phenotype BMC Cancer Neuroendocrine SI-NET SINET SBNET Neuroendocrine Small intestine |
| title | Exposure to nonanoic acid alters small intestinal neuroendocrine tumor phenotype |
| title_full | Exposure to nonanoic acid alters small intestinal neuroendocrine tumor phenotype |
| title_fullStr | Exposure to nonanoic acid alters small intestinal neuroendocrine tumor phenotype |
| title_full_unstemmed | Exposure to nonanoic acid alters small intestinal neuroendocrine tumor phenotype |
| title_short | Exposure to nonanoic acid alters small intestinal neuroendocrine tumor phenotype |
| title_sort | exposure to nonanoic acid alters small intestinal neuroendocrine tumor phenotype |
| topic | Neuroendocrine SI-NET SINET SBNET Neuroendocrine Small intestine |
| url | https://doi.org/10.1186/s12885-023-10722-8 |
| work_keys_str_mv | AT bilalalmobarak exposuretononanoicacidalterssmallintestinalneuroendocrinetumorphenotype AT vishalamlani exposuretononanoicacidalterssmallintestinalneuroendocrinetumorphenotype AT lindainge exposuretononanoicacidalterssmallintestinalneuroendocrinetumorphenotype AT tobiashofving exposuretononanoicacidalterssmallintestinalneuroendocrinetumorphenotype AT andreasmuth exposuretononanoicacidalterssmallintestinalneuroendocrinetumorphenotype AT olanilsson exposuretononanoicacidalterssmallintestinalneuroendocrinetumorphenotype AT martinjohansson exposuretononanoicacidalterssmallintestinalneuroendocrinetumorphenotype AT yvonnearvidsson exposuretononanoicacidalterssmallintestinalneuroendocrinetumorphenotype AT erikelias exposuretononanoicacidalterssmallintestinalneuroendocrinetumorphenotype |