Expression of glucagon‐like peptide 1 receptor in a murine C cell line Regulation of calcitonin gene by glucagon‐like peptide 1

Lamari, Y.; Boissard, Claudine; Moukhtar, M.S.; Jullienne, A.; Rosselin, G; Garel, Jean‐Michel

doi:10.1016/0014-5793(96)00895-2

Cited by 66 publications

(48 citation statements)

References 30 publications

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“…Recent data provide evidence that GLP-1 may play a role in the endocrine activity, growth, and differentiation of tumor cells. For instance, GLP-1 stimulated insulin secretion in human and rat insulinoma cell lines (29) and calcitonin secretion in a rat medullary thyroid carcinoma cell line (16,30). Furthermore, GLP-1 stimulated proliferation and inhibited apoptosis of insulinoma cells (29,31,32).…”

Section: Discussionmentioning

confidence: 98%

GLP-1 Receptor Expression in Human Tumors and Human Normal Tissues: Potential for In Vivo Targeting

Körner

Stöckli²,

Waser³

et al. 2007

Journal of Nuclear Medicine

406

303

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Peptide hormone receptors overexpressed in human tumors, such as somatostatin receptors, can be used for in vivo targeting for diagnostic and therapeutic purposes. A novel promising candidate in this field is the GLP-1 receptor, which was recently shown to be massively overexpressed in gut and lung neuroendocrine tumors-in particular, in insulinomas. Anticipating a major development of GLP-1 receptor targeting in nuclear medicine, our aim was to evaluate in vitro the GLP-1 receptor expression in a large variety of other tumors and to compare it with that in nonneoplastic tissues. Methods: The GLP-1 receptor protein expression was qualitatively and quantitatively investigated in a broad spectrum of human tumors (n 5 419) and nonneoplastic human tissues (n 5 209) with receptor autoradiography using 125 I-GLP-1(7-36)amide. Pharmacologic competition experiments were performed to provide proof of specificity of the procedure. Results: GLP-1 receptors were expressed in various endocrine tumors, with particularly high amounts in pheochromocytomas, as well as in brain tumors and embryonic tumors but not in carcinomas or lymphomas. In nonneoplastic tissues, GLP-1 receptors were present in generally low amounts in specific tissue compartments of several organs-namely, pancreas, intestine, lung, kidney, breast, and brain; no receptors were identified in lymph nodes, spleen, liver, or the adrenal gland. The rank order of potencies for receptor binding-namely, GLP-1(7-36)amide 5 exendin-4 GLP-2 5 glucagon(1-29)-provided proof of specific GLP-1 receptor identification. Conclusion: The GLP-1 receptors may represent a novel molecular target for in vivo scintigraphy and targeted radiotherapy for a variety of GLP-1 receptor-expressing tumors. For GLP-1 receptor scintigraphy, a low-background signal can be expected, on the basis of the low receptor expression in the normal tissues surrounding tumors. G protein-coupled peptide hormone receptors play an increasing role in cancer medicine. This role is based primarily on the peptide receptor overexpression on tumor cells, which allows specific receptor-targeted scintigraphic tumor imaging and tumor therapy with radiolabeled peptide analogs (1). The somatostatin receptors were the first peptide receptors identified for these purposes, and somatostatin receptor targeting has now become an integral part of the routine management of patients with gastroenteropancreatic neuroendocrine tumors. Somatostatin receptor scintigraphy (OctreoScan [ 111 In-pentetreotide]; Mallinckrodt, Inc.) detects these tumors with extremely high sensitivity and specificity (2). Moreover, recent results from clinical studies performing somatostatin receptor radionuclide therapy of these tumors are very promising (3,4).Prompted by the success of somatostatin receptor targeting, we have evaluated the overexpression of other peptide receptor families in tumors in vitro (1), with the aim, eventually, of being able to target in vivo a larger spectrum of tumors or individual tumors more efficiently with multiple pepti...

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Section: Discussionmentioning

confidence: 98%

GLP-1 Receptor Expression in Human Tumors and Human Normal Tissues: Potential for In Vivo Targeting

Körner

Stöckli²,

Waser³

et al. 2007

Journal of Nuclear Medicine

406

303

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“…There are indications that CCK 2 R is also expressed in normal parafollicular C cells (29). Glucagon-like peptide I also induces calcitonin mRNA in rat MTC cells (30).…”

Section: Discussionmentioning

confidence: 99%

The RET Kinase Inhibitor NVP-AST487 Blocks Growth and Calcitonin Gene Expression through Distinct Mechanisms in Medullary Thyroid Cancer Cells

et al. 2007

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The RET kinase has emerged as a promising target for the therapy of medullary thyroid cancers (MTC) and of a subset of papillary thyroid cancers. NVP-AST487, a N,N ¶-diphenyl urea with an IC 50 of 0.88 Mmol/L on RET kinase, inhibited RET autophosphorylation and activation of downstream effectors, and potently inhibited the growth of human thyroid cancer cell lines with activating mutations of RET but not of lines without RET mutations. NVP-AST487 induced a dose-dependent growth inhibition of xenografts of NIH3T3 cells expressing oncogenic RET, and of the MTC cell line TT in nude mice. MTCs secrete calcitonin, a useful indicator of tumor burden. Human plasma calcitonin levels derived from the TT cell xenografts were inhibited shortly after treatment, when tumor volume was still unchanged, indicating that the effects of RET kinase inhibition on calcitonin secretion were temporally dissociated from its tumor-inhibitory properties. Accordingly, NVP-AST487 inhibited calcitonin gene expression in vitro in TT cells, in part, through decreased gene transcription. These data point to a previously unknown physiologic role of RET signaling on calcitonin gene expression. Indeed, the RET ligands persephin and GDNF robustly stimulated calcitonin mRNA, which was blocked by pretreatment with NVP-AST487.

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“…GLP-1 has been shown to indirectly inhibit bone resorption via stimulation of calcitonin production induced by its binding to the GLP-1 receptor (GLP-1R) in thyroid C cells (28). Accordingly, mice with deletion of pancreatic GLP-1R develop cortical osteopenia and show increased bone resorption through a calcitonindependent pathway (29).…”

Section: Introductionmentioning

confidence: 99%

Chronic administration of Glucagon-like peptide-1 receptor agonists improves trabecular bone mass and architecture in ovariectomised mice

Pereira

Jeyabalan

Jorgensen

et al. 2015

Bone

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Expression of glucagon‐like peptide 1 receptor in a murine C cell line Regulation of calcitonin gene by glucagon‐like peptide 1

Cited by 66 publications

References 30 publications

GLP-1 Receptor Expression in Human Tumors and Human Normal Tissues: Potential for In Vivo Targeting

GLP-1 Receptor Expression in Human Tumors and Human Normal Tissues: Potential for In Vivo Targeting

The RET Kinase Inhibitor NVP-AST487 Blocks Growth and Calcitonin Gene Expression through Distinct Mechanisms in Medullary Thyroid Cancer Cells

Chronic administration of Glucagon-like peptide-1 receptor agonists improves trabecular bone mass and architecture in ovariectomised mice

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