Partial characterization of IR-α-MSH peptides found in melanoma tumors

Ghanem, G.; Loir, Béatrice; Hadley, Mac E.; Malek, Zalfa A. Abdel; Libert, Anita; Marmol, Véronique Del; Lejeune, Ferdinand; Lozano, Jesús Rodríguez; García-Borrón, J.C.

doi:10.1016/0196-9781(92)90060-g

Cited by 20 publications

(14 citation statements)

References 24 publications

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“…In agreement with the molecular mass range of immunoreactive a-melanotropin previously published (Ghanem et al, 1992) and after size fractionation of the extracts, most of the melanotropin immunoreactivity was repeatedly detected in the 1 -10-kDa fraction, both for melanoma and for the other positive tissue extracts (results not shown).…”

Section: Resultssupporting

confidence: 90%

“…Although the mechanism of the release needs further investigation, the hypothesis of an autocrine loop based on a-melanotropin and operating within malignant melanocytes is strongly supported by our data. This was also suggested in a previous report showing that a melanotropin-like immunoreactivity extracted from human melanoma metastases was able to displace 'Z'I-[Ahx4,~Phe7]melanotropin from its receptor, and to stimulate melanogenesis in mouse melanoma cells (Ghanem et al, 1989(Ghanem et al, , 1992. Here we show that the release of immunoreactive n-melanotropin from HBL cells is increased by several peptides able to bind to the melanocortin-I receptor.…”

Section: Discussionsupporting

confidence: 87%

“…Indeed, the relatively autonomous growth of malignant cells could be mediated, at least partially, by the production of their own growth factors (Sporn and Roberts, 1985). The hypothesis that melanoma tumour might behave as an ectopic source of immunoreactive amelanotropin was further strengthened by the finding of significant amounts of the latter not only in melanoma metastases but, more conclusively, in several melanoma cells grown in culture (Ghanem et al, 1989(Ghanem et al, , 1992. Moreover, the immunoreactive amelanotropin was partially purified and shown to be able to bind to a-melanotropin specific membrane receptors on melanoma cells, and stimulate melanogenesis (Ghanem et al, 1992).…”

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confidence: 99%

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Immunoreactive α‐Melanotropin as an Autocrine Effector in Human Melanoma Cells

Loir¹,

Bouchard²,

Morandini³

et al. 1997

European Journal of Biochemistry

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Melanotropin is a peptide having several functions, including the stimulation of melanogenesis and the modulation of proliferation of melanocytes and melanoma cells. It acts through binding to high-affinity receptors of the melanocortin-1 subtype, exclusively expressed in cells of the melanocytic lineage.Elevated levels of immunoreactive a-melanotropin were previously reported in melanoma cell lines, tumours and plasma from patients with melanoma. Here, we show that this high ectopic production of melanotropin is restricted to melanoma and non-pituitary tumours with the same neuroectodermic origin.The occurrence of a melanotropin-specific autocrine loop was further investigated in human melanoma cells. Immunoreactive a-melanotropin was spontaneously released from a melanoma cell line (HBL) expressing melanotropin receptors on the cell surface. This release was significantly increased in the presence of melanotropin-related peptides such as corticotropin-(4-10)-peptide and P-melanotropin, competing for binding to the melanotropin receptor and was directly correlated to the displacement potential of these peptides. Both spontaneous and induced releases of immunoreactive a-melanotropin could be blocked at low temperatures, suggesting the involvement of intracellular protein movement in the release mechanism.The release of immunoreactive a-melanotropin was not significant in melanoma cells expressing very low levels of melanotropin receptors (IGR3) or in non-melanoma cells (SCCI). However, upon expression of the melanocortin-I receptor cDNA into IGR3 cells, spontaneous and competition-induced releases of immunoreactive a-melanotropin were both increased and also blocked at low temperatures. This observation further underlines a role for the melanotropin receptor in the release of immunoreactive a-melanotropin. These experiments indicate that an autocrine loop between the melanocortin-1 receptor and immunoreactive a-melanotropin may be functional in human melanoma cells.

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Section: Resultssupporting

confidence: 90%

Section: Discussionsupporting

confidence: 87%

mentioning

confidence: 99%

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Immunoreactive α‐Melanotropin as an Autocrine Effector in Human Melanoma Cells

Loir¹,

Bouchard²,

Morandini³

et al. 1997

European Journal of Biochemistry

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“…POMC is expressed not only in the pituitary gland but also in a variety of nonpituitary organs and tumours including melanomas. [1][2][3] Our recent results showed that normal human melanocytes produce and secrete ␣-MSH and ACTH. 4 ␣-MSH has been reported to stimulate proliferation of melanoma cells and enhance their metastatic behaviour in the mouse model.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7][8] In a number of in vivo studies, extracts of metastasized melanoma were shown to contain ␣-MSH-like bioactive peptides as well as active MSH receptors. 2,3,9 Furthermore, elevated levels of circulating immunoreactive ␣-MSH were detected in patients with advanced melanomas. 10 ␣-, ␤and ␥-MSH were reported to be expressed in nodular type melanoma, 11 and in another study, ␤-MSH, ACTH and ␤-endorphin were detected in some cases of pigmented naevi and melanomas.…”

Section: Discussionmentioning

confidence: 99%

Immunoreactivity of alpha-melanocyte-stimulating hormone, adrenocorticotrophic hormone and beta-endorphin in cutaneous malignant melanoma and benign melanocytic naevi

et al. 1998

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Melanocyte-stimulating hormone (MSH) has been reported to enhance the experimental metastatic behaviour of melanoma cells in the mouse model. alpha-MSH production and MSH receptor (melanocortin 1 receptor gene) expression have been detected in cultured normal human melanocytes and metastasized melanomas. The exact role of MSH in the metastatic behaviour of human melanoma cells is, however, not yet known. To clarify a possible role of proopiomelanocortin (POMC)-derived peptides, including alpha-MSH, in melanoma development and progression, we analysed immunohistochemically the localization of alpha-MSH adrenocorticotrophic hormone (ACTH) and beta-endorphin in various kinds of benign pigmented naevocytic lesions and malignant melanomas. Three of 21 samples of common and dysplastic naevi showed detectable alpha-MSH staining in naevus cells, and five and six of 15 samples were weakly positive for ACTH and beta-endorphin staining, respectively. In melanoma samples, 24 of 45, 23 of 39 and 30 of 42 samples showed positive staining with alpha-MSH, ACTH and beta-endorphin antibodies, respectively. Furthermore, staining for all three antibodies was noted to be more intense and diffuse in samples of nodular melanoma, vertically growing acral lentiginous melanoma and superficial spreading melanoma as well as metastatic lesions compared with those of naevi. Although it is yet to be determined whether or not this strong staining for POMC-derived peptides in advanced melanoma cells indicates a role of autocrine or paracrine regulation, our results suggest a possible involvement of POMC gene products in melanoma progression.

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Modulation of ICAM-1 expression by α-MSH in human melanoma cells and melanocytes

et al. 1998

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Alpha-MSH, a proopiomelanocortin (POMC)-derived peptide, is known to be produced in the pituitary, the skin, and melanoma tumors and to possess many biological effects, mainly on melanocyte pigmentation and growth. Moreover, the melanocyte expresses adhesion molecules, including ICAM-1. The latter has been reported to play a role in melanoma spread and associated metastatic process. We conducted a study in order to evaluate the possible effect of MSH on ICAM-1 expression in human cultured malignant and normal melanocytes. Our data show that alpha-MSH inhibits ICAM-1 expression stimulated by TNF in a concentration-dependent manner, both at the protein and gene expression level. Ninety percent inhibition was obtained with 10 nM MSH, while 50% inhibition was achieved with 1 nM. Endogenous cAMP elevation with forskolin as well as an exogenous cAMP stable analogue (Sp-cAMPS) produced the same inhibitory effect. A screening of malignant melanocytes showed that inhibition of ICAM-1 expression could be achieved only in those cells expressing detectable MSH receptors and seemed to correlate with the number of binding sites. In conclusion, our data strongly suggest alpha-MSH as a potent inhibitor of ICAM-1 expression in malignant melanocytes acting through MSH receptor stimulation and subsequent cAMP increase.

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Partial characterization of IR-α-MSH peptides found in melanoma tumors

Cited by 20 publications

References 24 publications

Immunoreactive α‐Melanotropin as an Autocrine Effector in Human Melanoma Cells

Immunoreactive α‐Melanotropin as an Autocrine Effector in Human Melanoma Cells

Immunoreactivity of alpha-melanocyte-stimulating hormone, adrenocorticotrophic hormone and beta-endorphin in cutaneous malignant melanoma and benign melanocytic naevi

Modulation of ICAM-1 expression by α-MSH in human melanoma cells and melanocytes

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