Granins and granin-related peptides in neuroendocrine tumours

Portela-Gomes, Guida Maria; Grimelius, Lars; Wilander, Erik; Stridsberg, Mats

doi:10.1016/j.regpep.2010.02.011

Cited by 47 publications

(44 citation statements)

References 140 publications

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“…CgA is present in the serum of normal subjects at about 1 nmol/L levels (25). Higher circulating levels (in the nanomolar range) have been detected in patients with neuroendocrine tumors and in subpopulations of patients with breast cancer, prostate cancer, small and nonsmall cell lung cancer (11,(26)(27)(28), or in patients with heart failure, renal failure, hypertension, rheumatoid arthritis, giant cell arthritis, sepsis, and atrophic gastritis, or treated with proton pump inhibitors (9,25,26,29,30). Thus, the doses used in this study are biologically relevant as they are in the range of those found in patients with nonneuroendocrine tumors.…”

Section: Discussionmentioning

confidence: 99%

Chromogranin A Regulates Tumor Self-Seeding and Dissemination

Dondossola¹,

Crippa²,

Colombo³

et al. 2012

Cancer Research

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Cancer progression involves the seeding of malignant cells in circulation and the colonization of distant organs. However, circulating neoplastic cells can also reinfiltrate the tumor of origin. This process, called "tumor-self seeding," can select more aggressive cells that may contribute to cancer progression. Here, using mouse mammary adenocarcinoma models, we observed that both tumor self-seeding and organ colonization were inhibited by chromogranin A (CgA), a protein present in variable amounts in the blood of cancer patients. Mechanism studies showed that CgA inhibited the shedding of cancer cells in circulation from primary tumors, as well as the reinfiltration of tumors and the colonization of lungs by circulating tumor cells. CgA reduced gap formation induced by tumor cell-derived factors in endothelial cells, decreased vascular leakage in tumors, and inhibited the transendothelial migration of cancer cells. Together, our findings point to a role for circulating CgA in the regulation of tumor cell trafficking from tumor-to-blood and from blood-to-tumor/normal tissues. Inhibition of the multidirectional trafficking of cancer cells in normal and neoplastic tissues may represent a novel strategy to reduce cancer progression. Cancer Res; 72(2); 449-59. Ó2011 AACR.

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Section: Discussionmentioning

confidence: 99%

Chromogranin A Regulates Tumor Self-Seeding and Dissemination

Dondossola¹,

Crippa²,

Colombo³

et al. 2012

Cancer Research

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“…Moreover, while granin-derived peptides have been reported to be produced in pheochromocytoma (e.g. pancreastatin, chromacin, WE14, EL35 from CGA; GAWK from CGB; SN from SgII), they rarely distinguished the two types of pheochromocytoma (for reviews, see Conlon (2010), Guerin et al (2010) and Portela-Gomes et al (2010)). Our study indicates that EM66 measurement discriminates between benign and malignant tumors with a high accuracy.…”

Section: Discussionmentioning

confidence: 99%

“…The role of the different SgII-derived peptides generated deserves further investigation. These peptides are known to be produced through the action of the prohormone convertases PC1 and PC2 (Dittie & Tooze 1995, Hoflehner et al 1995, Laslop et al 1998, which, like granins, may constitute markers of neuroendocrine tumors (Scopsi et al 1995, Portela-Gomes et al 2010. Several studies have reported the expression of PC1 and PC2 in normal adrenal glands and pheochromocytomas by northern blot, RT-PCR, and immunohistochemistry (Konoshita et al 1994, Scopsi et al 1995.…”

Section: Discussionmentioning

confidence: 99%

“…The ubiquitous distribution of granins and their derived peptides in nervous, endocrine, and neuroendocrine tissues makes these entities useful markers of secretion from neuroendocrine cells and neoplasms (Rosa & Gerdes 1994). Thus, Cgs/Sgs and Cgs/Sgs-derived peptides may be used for the diagnosis and/or prognosis of neuroendocrine tumors (Conlon 2010, Portela-Gomes et al 2010. For instance, high concentrations of SgII were found in ganglioneuromas and neuroblastomas (Eder et al 1998), and high plasma SN concentrations were associated with several neuroendocrine tumors (Ischia et al 2000a, Stridsberg et al 2008 or progression of neuroendocrine prostatic carcinomas (Ischia et al 2000b).…”

Section: Introductionmentioning

confidence: 99%

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Differential expression and processing of secretogranin II in relation to the status of pheochromocytoma: implications for the production of the tumoral marker EM66

Guillemot¹,

Thouennon²,

Guérin³

et al. 2012

Journal of Molecular Endocrinology

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We have previously demonstrated that measurement of tissue concentrations of the secretogranin II (SgII or SCG2 as listed in the HUGO database)-derived peptide EM66 may help to discriminate between benign and malignant pheochromocytomas and that EM66 represents a sensitive plasma marker of pheochromocytomas. Here, we investigated the gene expression and protein production of SgII in 13 normal adrenal glands, and 35 benign and 16 malignant pheochromocytomas with the goal to examine the molecular mechanisms leading to the marked variations in the expression of EM66 in tumoral chromaffin tissue. EM66 peptide levels were 16-fold higher in benign than in malignant pheochromocytomas and had an area under the receiver-operating characteristic curve of 0 . 95 for the distinction of benign and malignant tumors. Q-PCR experiments indicated that the SgII gene was significantly underexpressed in malignant tumors compared with benign tumors. Western blot analysis using antisera directed against SgII and SgII-derived fragments revealed lower SgII protein and SgII-processing products in malignant tumors. Western blot also showed that low p-cAMP-responsive element-binding (CREB) concentrations seemed to be associated with the malignant status. In addition, the prohormone convertase PC1 and PC2 genes and proteins were overexpressed in benign pheochromocytomas compared with malignant pheochromocytomas. Low concentrations of EM66 found in malignant tumors are associated with reduced expression and production of SgII and SgII-derived peptides that could be ascribed to a decrease in SgII gene transcription, probably linked to p-CREB down-regulation, and to lower PC levels. These findings highlight the mechanisms leading to lower concentrations of EM66 in malignant pheochromocytoma and strengthen the notion that this peptide is a suitable marker of this neuroendocrine tumor.

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“…SGs also contain granin-family proteins and membrane-associated prohormone processing enzymes. The granin family consists of seven types of acidic secretory proteins: chromogranin A (CgA), chromogranin B (also known as secretogranin I; SgI), SgII (also known as chromogranin C), and SgIII-VI proteins (Huttner et al 1991;Taupenot et al 2003; 575032J HCXXX10.1369/0022155415575032Gomi et alSecretogranin III in Chicken Endocrine Cells research-article2015 Portela-Gomes et al 2010;Bartolomucci et al 2011). Although the functions of granin-family proteins are not completely understood, recent findings have suggested their involvement in several processes.…”

Section: Introductionmentioning

confidence: 99%

Expression of Secretogranin III in Chicken Endocrine Cells

Gomi

Morikawa

Shinmura

et al. 2015

J Histochem Cytochem.

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The expression of secretogranin III (SgIII) in chicken endocrine cells has not been investigated. There is limited data available for the immunohistochemical localization of SgIII in the brain, pituitary, and pancreatic islets of humans and rodents. In the present study, we used immunoblotting to reveal the similarities between the expression patterns of SgIII in the common endocrine glands of chickens and rats. The protein–protein interactions between SgIII and chromogranin A (CgA) mediate the sorting of CgA/prohormone core aggregates to the secretory granule membrane. We examined these interactions using co-immunoprecipitation in chicken endocrine tissues. Using immunohistochemistry, we also examined the expression of SgIII in a wide range of chicken endocrine glands and gastrointestinal endocrine cells (GECs). SgIII was expressed in the pituitary, pineal, adrenal (medullary parts), parathyroid, and ultimobranchial glands, but not in the thyroid gland. It was also expressed in GECs of the stomach (proventriculus and gizzard), small and large intestines, and pancreatic islet cells. These SgIII-expressing cells co-expressed serotonin, somatostatin, gastric inhibitory polypeptide, glucagon-like peptide-1, glucagon, or insulin. These results suggest that SgIII is expressed in the endocrine cells that secrete peptide hormones, which mature via the intragranular enzymatic processing of prohormones and physiologically active amines in chickens.

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Granins and granin-related peptides in neuroendocrine tumours

Cited by 47 publications

References 140 publications

Chromogranin A Regulates Tumor Self-Seeding and Dissemination

Chromogranin A Regulates Tumor Self-Seeding and Dissemination

Differential expression and processing of secretogranin II in relation to the status of pheochromocytoma: implications for the production of the tumoral marker EM66

Expression of Secretogranin III in Chicken Endocrine Cells

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