Immunohistochemical evidence of α-, β- and γ3-melanocyte stimulating hormone expression in cutaneous malignant melanoma of nodular type

Liu, Peng Yue; Johansson, Ӧlle

doi:10.1016/0923-1811(95)00405-h

Cited by 17 publications

(12 citation statements)

References 35 publications

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“…They proposed a possibility that melanoma cells might autonomously produce MSHs secreted into blood circulation and among the cells to promote self-proliferation, extending to the perilesional tissue. They speculated another possibility that the perilesional tissues could synthesize MSH peptides due to the effect of proliferation of melanoma cells (21). In this study, tumor cells expressed CRH and POMC peptides strongly; therefore, POMC peptides in the perilesional tissue might be produced locally underlying a cross-talk between the tumor cells and perilesional cells.…”

Section: Discussionmentioning

confidence: 97%

In situexpression of corticotropin‐releasing hormone (CRH) and proopiomelanocortin (POMC) genes in human skin

Kono¹,

Nagata²,

Umemura³

et al. 2001

FASEB j.

108

100

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Systemic stresses induce corticotropin-releasing hormone (CRH) expression in hypothalamus. CRH is released to the pituitary gland, where it stimulates proopiomelanocortin (POMC) production acting via the CRH receptor (CRH-R). CRH and POMC peptides are also detected in sites outside of the central nervous system (CNS), such as the skin. However, it has not been elucidated whether these peptides detected in the skin are derived from CNS or are produced locally. Using immunohistochemical and in situ reverse-transcription (RT)-PCR techniques, we demonstrated coexpression of CRH and POMC mRNAs in the epidermis and pilosebaceous units of the human skin. This coexpression was confirmed by the combination of laser-capture microdissection (LCM) with RT-PCR, analyzing mRNA expressions in captured sebaceous cells. Immunoreactivities and expressions of CRH and POMC mRNAs were strong in inflammatory lesions, melanocytic nevus, seborrheic keratosis, and also in the periphery of the benign tumor. These findings suggest that CRH and POMC peptides are produced locally in the skin and are regulated by inflammatory cells as well as by autocrine mechanisms. The skin may have "a local stress response system," whose activity is mediated by CRH and POMC peptides, in an equivalent to hypothalamus-pituitary adrenal axis.

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Section: Discussionmentioning

confidence: 97%

In situexpression of corticotropin‐releasing hormone (CRH) and proopiomelanocortin (POMC) genes in human skin

Kono¹,

Nagata²,

Umemura³

et al. 2001

FASEB j.

108

100

View full text Add to dashboard Cite

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“…In sebaceous glands, α-, β- and γ 3 -MSH immunoreactivity were only detected in regions adjacent to a pathologic process, i.e. cutaneous melanomas suggesting a reactive phenomenon [12]. …”

Section: The Skin As a Factory Of Melanocortinsmentioning

confidence: 99%

“…MCs have been found to be overexpressed in a variety of neoplastic and inflammatory skin disorders including melanocytic naevi, melanoma, basal cell carcinoma, squamous cell carcinoma, keloids, psoriasis, scarring alopecia and acute UV dermatitis [9, 12, 69, 70]. Regarding pigment lesions immunoreactivity of α-MSH, ACTH and β-ED was more intense and diffuse in samples of nodular melanoma, vertically growing acral lentiginous melanoma, superficial spreading melanoma and metastatic melanomas compared to nevi.…”

Section: Melanocortin and Melanocortin Receptor Expression In Diseasementioning

confidence: 99%

The Role of Melanocortins in Skin Homeostasis

Böhm¹,

Luger²

2000

Horm Res Paediatr

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Melanocortins are structurally related bioactive peptides which are produced by many extra-neural tissues including the skin. All of the melanocortins (α, β, and γ-melanocyte-stimulating hormone and adrenocorticotropin) have melanotropic activity but can elicit many other effects on skin cells. On the basis of in vitro and in vivo findings melanocortins have been shown to regulate immune and inflammatory responses, hair growth, exocrine gland activity and extracellular matrix composition. These effects are mediated by melanocortin receptors among which the melanocortin-1 receptor is most ubiquitously expressed by human skin cells. Simultaneous expression of melanocortins and their receptors suggest a complex autocrine and/or paracrine regulatory network whose disruption invariably affects skin homeostasis. Expression of melanocortin receptors on various skin cell types further indicates novel pharmacological targets for the treatment of skin diseases.

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“…Melanoma patients show high levels of a-MSH in plasma and tumours (Ghanem et al, 1989a, b), thought to correlate with malignant melanoma development (Liu and Johansson, 1995). However, a-MSH is reported to both stimulate and inhibit melanoma invasion in vitro and in vivo.…”

mentioning

confidence: 99%

Anti-inflammatory and anti-invasive effects of α-melanocyte-stimulating hormone in human melanoma cells

et al. 2003

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a-Melanocyte stimulating hormone (a-MSH) is known to have pleiotrophic functions including pigmentary, anti-inflammatory, antipyretic and immunoregulatory roles in the mammalian body. It is also reported to influence melanoma invasion with levels of a-, b-and g-MSH correlated clinically with malignant melanoma development, but other studies suggest a-MSH acts to retard invasion. In the present study, we investigated the action of a-MSH on three human melanoma cell lines (HBL, A375-SM and C8161) differing in metastatic potential. a-melanocyte-simulating hormone reduced invasion through fibronectin and also through a human reconstructed skin composite model for the HBL line, and inhibited proinflammatory cytokine-stimulated activation of the NF-kB transcription factor. However, A375-SM and C8161 cells did not respond to a-MSH. Immunofluorescent microscopy and Western blotting identified melanocortin-1 receptor (MC-1R) expression for all three lines and MC-2R on HBL and A375-SM lines. Receptor binding identified a similar affinity for a-MSH for all three lines with the highest number of binding sites on HBL cells. Only the HBL melanoma line demonstrated a detectable cyclic adenosine monophosphate (cAMP) response to a-MSH, although all three lines responded to acute a-MSH addition ( þ (À)-N 6 -(2-phenylisopropyl)-adenosine (PIA)) with an elevation in intracellular calcium. The nonresponsive lines displayed MC-1R polymorphisms (C8161, Arg (wt) 151/Cys 151; A375-SM, homozygous Cys 151), whereas the HBL line was wild type. Stable transfection of the C8161 line with wild-type MC-1R produced cells whose invasion was significantly inhibited by a-MSH. From this data, we conclude that a-MSH can reduce melanoma cell invasion and protect cells against proinflammatory cytokine attack in cells with the wild-type receptor (HBL).

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Immunohistochemical evidence of α-, β- and γ3-melanocyte stimulating hormone expression in cutaneous malignant melanoma of nodular type

Cited by 17 publications

References 35 publications

In situexpression of corticotropin‐releasing hormone (CRH) and proopiomelanocortin (POMC) genes in human skin

In situexpression of corticotropin‐releasing hormone (CRH) and proopiomelanocortin (POMC) genes in human skin

The Role of Melanocortins in Skin Homeostasis

Anti-inflammatory and anti-invasive effects of α-melanocyte-stimulating hormone in human melanoma cells

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