ArticleEndocrine connections2022
Aberrant tryptophan metabolism in stromal cells is associated with mesenteric fibrosis in small intestinal neuroendocrine tumors.
Article in Endocrine connections, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
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Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.
- Mesenteric Fibrosis in Neuroendocrine Neoplasms: a Systematic Review of New Thoughts on Causation and Potential Treatments.Current oncology reports · 2025Pooled it
- Unravelling mesenteric fibrosis in small intestinal neuroendocrine tumours and implications for clinical management.Endocrine-related cancer · 2026Review
- Tryptophan metabolism in tumor immune escape: mechanisms, cellular crosstalk, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Telotristat ethyl affects tumour-fibroblast crosstalk in small intestinal neuroendocrine tumours.Journal of neuroendocrinology · 2025Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Increased levels of serotonin secretion are associated with mesenteric fibrosis (MF) in small intestinal neuroendocrine tumors (SI-NETs). However, the profibrotic potential of serotonin differs between patients, and in this study, we aimed to gain an understanding of the mechanisms underlying this variability. To this end, we analyzed the proteins involved in tryptophan metabolism in SI-NETs. Methods: Proteomes of tumor and stroma from primary SI-NETs and paired mesenteric metastases of patients with MF (n = 6) and without MF (n = 6) were identified by liquid chromatography-mass spectrometry (LC-MS). The differential expression of proteins involved in tryptophan metabolism between patients with and without MF was analyzed. Concurrently, monoamine oxidase A (MAO-A) expression was analyzed in the tumor and stromal compartment by immunohistochemistry (IHC) and reported as intensity over area (I/A). Results: Of the 42 proteins involved in tryptophan metabolism, 20 were detected by LC-MS. Lower abundance of ten proteins was found in mesenteric metastases stroma in patients with MF. No differential expression was found in primary SI-NETs. In patients with MF, IHC showed lower MAO-A expression in the stroma of the primary SI-NETs (median 4.2 I/A vs 6.5 I/A in patients without MF, P = 0.003) and mesenteric metastases (median 2.1 I/A vs 2.8 I/A in patients without MF, P= 0.019). Conclusion: We found a decreased expression of tryptophan and serotonin-metabolizing enzymes in the stroma in patients with MF, most notably in the mesenteric stroma. This might account for the increased profibrotic potential of serotonin and explain the variability in the development of SI-NET-associated fibrotic complications.
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