Expression of trophic amidated peptides and their receptors in benign and malignant pheochromocytomas: high expression of adrenomedullin RDC1 receptor and implication in tumoral cell survival

Thouënnon, Erwan; Aimar, Pierre; Tanguy, Yannick; Guillemot, Johann; Manecka, Destiny-Love; Guérin, M; Ouafik, L’Houcine; Mureşan, Mihaela; Klein, Marc; Bertherat, Jérôme; Lefebvre, Henri; Plouin, Pierre‐François; Yon, Laurent; Anouar, Youssef

doi:10.1677/erc-10-0109

Cited by 19 publications

(34 citation statements)

References 55 publications

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“…Membrane-associated CXCR7 is expressed on a number of tumor cell lines, activated endothelial cells and fetal liver cells, but is absent on other cell types (4). A receptor exhibited a four-fold higher expression in malignant pheochromocytomas compared with benign ones (5). Ectopic CXCR7 expression in NIH 3T3 cells significantly increased cell proliferation and formed tumors when xenografted in nude mice (10).…”

Section: Discussionmentioning

confidence: 99%

Role of CXC chemokine receptor type 7 in carcinogenesis and lymph node metastasis of colon cancer

Wang¹,

Lin²,

Qi³

et al. 2015

Molecular and Clinical Oncology

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Abstract. Upregulated expression of the CXC chemokine receptor type 7 (CXCR7) promotes breast, lung and prostate cancer progression and metastasis. However, the role of CXCR7 in colon cancer has not been determined. We hypothesized that increased CXCR7 expression may contribute to human colon cancer occurrence and progression. Reverse transcription quantitative polymerase chain reaction and western blot analysis were performed on 34 malignant and 18 normal colon tissue specimens. The specimens were obtained from 19 male and 15 female patients, with a mean age of 52 years (range, 34-79 years). Of the 34 patients, 20 had lymph node metastases. None of the patients had received adjuvant radiotherapy or chemotherapy prior to surgery. This study demonstrated that CXCR7 levels were significantly higher in colon tumors compared with those in normal colon tissue (P﹤0.01). In addition, lymph node metastatic colon tumors exhibited significantly higher CXCR7 expression compared with non-metastatic tumors (P﹤0.01); however, there were no differences in CXCR7 expression among distinct histopathological types (well-differentiated vs. moderately-to-poorly differentiated adenocarcinoma, P﹥0.01). Therefore, the evidence obtained from the present study supports involvement of the upregulated CXCR7 expression in colon tumorigenesis and lymph node metastasis.

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Section: Discussionmentioning

confidence: 99%

Role of CXC chemokine receptor type 7 in carcinogenesis and lymph node metastasis of colon cancer

Wang¹,

Lin²,

Qi³

et al. 2015

Molecular and Clinical Oncology

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“…The expression of CGRP receptor components and CGRP activity has been examined in several tumours and tumour-derived cell lines. For example, RAMP1 mRNA expression has been detected in benign and malignant pheochromocytomas (Thouennon et al 2010), Conn's adenoma (Forneris et al 2001) and pancreatic cancers (Ramachandran et al 2007).…”

Section: C5mentioning

confidence: 99%

“…In the original publication, it was reported that RDC1 could also bind AM with low affinity (200 nM). This seems to have generated the notion that RDC1 is a putative AM receptor (Thouennon et al 2010). There has been no independent verification that RDC1 can bind AM and until it can be demonstrated that RDC1 can produce a functional response inside a cell on binding AM, it cannot be considered as an AM receptor.…”

Section: L Hay Et Al: Am and Cgrp In Endocrine-related Cancersmentioning

confidence: 99%

“…There has been no independent verification that RDC1 can bind AM and until it can be demonstrated that RDC1 can produce a functional response inside a cell on binding AM, it cannot be considered as an AM receptor. There are reports in the literature that AM signalling and the presence of RDC1 are associated but this correlation does not mean that RDC1 is a receptor for AM (Autelitano & Tang 1999, Chakravarty et al 2000, Ladoux & Frelin 2000, Sierro et al 2007, Thouennon et al 2010. There are many possible explanations, such as regulation of CLR and/or RAMP expression, for example.…”

Section: L Hay Et Al: Am and Cgrp In Endocrine-related Cancersmentioning

confidence: 99%

“…Of course, there is not always a simple relationship between mRNA and protein expression. Indeed, it has sometimes been argued that low expression of CLR or RAMPs is a sign that these are not involved in an AM-mediated response (Thouennon et al 2010). However, even if low mRNA can be equated with low expression of protein, it does not need high expression of a GPCR to produce a response.…”

Section: L Hay Et Al: Am and Cgrp In Endocrine-related Cancersmentioning

confidence: 99%

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Adrenomedullin and calcitonin gene-related peptide receptors in endocrine-related cancers: opportunities and challenges

Hay

Walker²,

Poyner³

2010

Endocrine Related Cancer

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Adrenomedullin (AM), adrenomedullin 2 (AM2/intermedin) and calcitonin gene-related peptide (CGRP) are members of the calcitonin family of peptides. They can act as growth or survival factors for a number of tumours, including those that are endocrine-related. One mechanism through which this occurs is stimulating angiogenesis and lymphangiogenesis. AM is expressed by numerous tumour types and for some cancers, plasma AM levels can be correlated with the severity of the disease. In cancer models, lowering AM content or blocking AM receptors can reduce tumour mass. AM receptors are complexes formed between a seven transmembrane protein, calcitonin receptor-like receptor and one of the two accessory proteins, receptor activity-modifying proteins (RAMPs) 2 or 3 to give the AM 1 and AM 2 receptors respectively. AM also has affinity at the CGRP receptor, which uses RAMP1. Unfortunately, due to a lack of selective pharmacological tools or antibodies to distinguish AM and CGRP receptors, the precise receptors and signal transduction pathways used by the peptides are often uncertain. Two other membrane proteins, RDC1 and L1/G10D (the 'ADMR'), are not currently considered to be genuine CGRP or AM receptors. In order to properly evaluate whether AM or CGRP receptor inhibition has a role in cancer therapy, it is important to identify which receptors mediate the effects of these peptides. To effectively distinguish AM 1 and AM 2 receptors, selective receptor antagonists need to be developed. The development of specific CGRP receptor antagonists suggests that this is now feasible.

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Expression of Trophic Peptides and Their Receptors in Chromaffin Cells and Pheochromocytoma

et al. 2010

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Pheochromocytomas are catecholamine-producing tumors arising from chromaffin cells of the adrenal medulla or extra-adrenal location. Along with catecholamines, tumoral cells produce and secrete elevated quantities of trophic peptides which are normally released in a regulated manner by the normal adrenal medulla. Among these peptides, the amounts of pituitary adenylate cyclase-activating polypeptide (PACAP), adrenomedullin (AM), and neuropeptide Y (NPY) are particularly high. These peptides can exert endocrine, paracrine or autocrine effects in numerous cell types. In particular, they have been shown to be involved in cell proliferation and survival, catecholamine production and secretion, and angiogenesis. Some of these processes are exacerbated in pheochromocytomas, raising the possibility of the involvement of trophic peptides. Here, we review the expression levels of NPY, PACAP, and AM and theirs receptors in chromaffin cells and pheochromocytomas, and address their possible implication in the adrenal medulla tumorigenesis and malignant development of pheochromocytomas.

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Expression of trophic amidated peptides and their receptors in benign and malignant pheochromocytomas: high expression of adrenomedullin RDC1 receptor and implication in tumoral cell survival

Cited by 19 publications

References 55 publications

Role of CXC chemokine receptor type 7 in carcinogenesis and lymph node metastasis of colon cancer

Role of CXC chemokine receptor type 7 in carcinogenesis and lymph node metastasis of colon cancer

Adrenomedullin and calcitonin gene-related peptide receptors in endocrine-related cancers: opportunities and challenges

Expression of Trophic Peptides and Their Receptors in Chromaffin Cells and Pheochromocytoma

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