ArticlePloS one2013
Chromogranin A and its fragments as regulators of small intestinal neuroendocrine neoplasm proliferation.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Stress, Well-Being, and Reproduction in Wildlife.Advances in experimental medicine and biology · 2026Review
- Case Report: Postoperative cervical lymph node metastasis of the neuroendocrine carcinoma component of rectal mixed adenoneuroendocrine carcinoma.Frontiers in oncology · 2025Article
- Cellular mechanisms of hormone secretion in neuroendocrine tumors: what goes wrong?Frontiers in cell and developmental biology · 2025Review
- Comparison of clinicopathological characteristics and survival outcomes between solitary and multiple rectal neuroendocrine tumors: a propensity score-matched study.Frontiers in oncology · 2025Article
- Co-Expression of Adaptor Protein FAM159B with Different Markers for Neuroendocrine Cells: An Immunocytochemical and Immunohistochemical Study.International journal of molecular sciences · 2022Article
- Role of chromogranin A-derived fragments after resection of nonfunctioning pancreatic neuroendocrine tumors.Journal of endocrinological investigation · 2022Article
- Effect of chromogranin A N-terminal fragment vasostatin-1 nano-carrier transfection on abdominal aortic aneurysm formation.Bioengineered · 2021Article
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- Vasostatin-1: A novel circulating biomarker for ileal and pancreatic neuroendocrine neoplasms.PloS one · 2018Article
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- c-MYC drives histone demethylase PHF8 during neuroendocrine differentiation and in castration-resistant prostate cancer.Oncotarget · 2016Article
- Identification of 5-hydroxytryptamine-producing cells by detection of fluorescence in paraffin-embedded tissue sections.European journal of histochemistry : EJH · 2016Article
- Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging.Oncotarget · 2016Article
- Multimodal Somatostatin Receptor Theranostics Using [(64)Cu]Cu-/[(177)Lu]Lu-DOTA-(Tyr(3))octreotate and AN-238 in a Mouse Pheochromocytoma Model.Theranostics · 2016Article
- Decoding the Molecular and Mutational Ambiguities of Gastroenteropancreatic Neuroendocrine Neoplasm Pathobiology.Cellular and molecular gastroenterology and hepatology · 2015Review
- Prostate cancer and neuroendocrine differentiation: more neuronal, less endocrine?Frontiers in oncology · 2015Review
- Biological function and clinical relevance of chromogranin A and derived peptides.Endocrine connections · 2014Article
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Authors and funding
7 authors at 2 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionChromogranin A is a neuroendocrine secretory product and its loss is a feature of malignant NEN de-differentiation. We hypothesized that chromogranin A fragments were differentially expressed during NEN metastasis and played a role in the regulation of NEN proliferation.
methodsChromogranin A mRNA (PCR) and protein (ELISA/western blot) were studied in 10 normal human mucosa, 5 enterochromaffin cell preparations, 26 small intestinal NEN primaries and 9 liver metastases. Cell viability (WST-1 assay), proliferation (bromodeoxyuridine ELISA) and expression of AKT/AKT-P (CASE ELISA/western blot) in response to chromogranin A silencing, inhibition of prohormone convertase and mTOR inhibition (RAD001/AKT antisense) as well as different chromogranin A fragments were examined in 4 SI-NEN cell lines.
resultsChromogranin A mRNA and protein levels were increased (37-340 fold, p<0.0001) in small intestinal NENs compared to normal enterochromaffin cells. Western blot identified chromogranin A-associated processing bands including vasostatin in small intestinal NENs as well as up-regulated expression of prohormone convertase in metastases. Proliferation in small intestinal NEN cell lines was decreased by silencing chromogranin A as well as by inhibition of prohormone convertase (p<0.05). This inhibition also decreased secretion of chromogranin A (p<0.05) and 5-HT (p<0.05) as well as expression of vasostatin. Metastatic small intestinal NEN cell lines were stimulated (50-80%, p<0.05) and AKT phosphorylated (Ser473: p<0.05) by vasostatin I, which was completely reversed by RAD001 (p<0.01) and AKT antisense (p<0.05) while chromostatin inhibited proliferation (~50%, p<0.05).
conclusionChromogranin A was differentially regulated in primary and metastatic small intestinal NENs and cell lines. Chromogranin A fragments regulated metastatic small intestinal NEN proliferation via the AKT pathway indicating that CgA plays a far more complex role in the biology of these tumors than previously considered.
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