MSH RECEPTOR EXPRESSION AND THE RELATIONSHIP TO MELANOGENESIS AND METASTATIC ACTIVITY IN B16 MELANOMA

被引：37

作者：

LUNEC, J

PIERON, C

THODY, AJ

机构：

[1] Cancer Research Unit, University of Newcastle upon Tyne Medical School, Newcastle upon Tyne

[2] Department of Dermatology, University of Newcastle upon Tyne Medical School, Newcastle upon Tyne

来源：

MELANOMA RESEARCH | 1992年 / 2卷 / 01期

关键词：

ACTH; MELANOGENESIS; METASTASIS; MELANOMA; ALPHA-MSH; ALPHA-MSH RECEPTORS; POMC PEPTIDES;

D O I：

10.1097/00008390-199205000-00002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

In this study we have compared the effects of different pro-opiomelanocortin (POMC) peptides on melanogenesis and metastasis and their relationship to MSH receptor expression in B16F1 melanoma cells. All peptides, apart from beta-endorphin, increased melanogenesis and the order of potency was Nle4DPhe7-alpha-MSH>alpha-MSH>ACTH[1-39]>des-acetyl alpha-MSH>ACTH[1-24]. A similar order of potency was found for metastasis, except for ACTH [1-24], which had a relatively greater effect on metastasis. These findings suggest that the effects on melanogenesis and metastasis are mediated via the same receptor. The results of ligand binding studies also indicated the presence of a single receptor with a K(D) value for Nle4DPhe7-alpha-MSH of 62+/-16pM. This was consistent with crosslinking studies using [I-125] Nle4DPhe7-alpha-MSH which produced a single 50-55 kD band on analysis by SDS-PAGE. However, the relative binding affinities of the different peptides, measured by displacement of [I-125]-Nle4DPhe7-alpha-MSH, did not closely correlate with the relative potencies in stimulating melanogenesis and metastasis. This suggests that receptor activation and the subsequent biological response is not determined solely by binding affinity.

引用

页码：5 / 12

页数：8

共 25 条

[1]

Liotta L.A., Tumour invasion and metastasis-role of the extracellular matrix. Rhoads Memorial Award Lecture, Cancer Res, 46, pp. 1-7, (1986)

[2]

Sheppard J.R., Koestler J.P., Corwin S.P., Et al., Experimental metastasis correlates with cyclic AMP accumulation in B16 melanoma clones, Nature, 308, pp. 544-547, (1984)

[3]

Bennett D.C., Dexter T.J., Ormerod E.J., Et al., Increased experimental metastatic capacity of a murine melanoma following induction of differentiation, Cancer Res, 46, pp. 3239-3244, (1986)

[4]

Halaban R., Pomerantz S.H., Marshall S., Et al., Regulation of tyrosinase in human melanocytes grown in culture, J Cell Biol, 97, pp. 480-488, (1983)

[5]

Ghanem G.E., Comunale G., Libert A., Et al., Evidence for a-melanocyte stimulating hormone (α-MSH) receptors on human malignant melanoma cells, Int J Cancer, 41, pp. 248-255, (1988)

[6]

Siegrist W., Oestreicher M., Stutz S., Et al., Radioreceptor assay for α-MSH using B16 melanoma cells, J Receptor Res, 8, pp. 323-343, (1988)

[7]

Siegrist W., Solca F., Stutz S., Et al., Characterization of receptors for α-melanotropin (α-MSH) in human melanoma cells, Cancer Res, 49, pp. 6352-6358, (1989)

[8]

Solca F., Siegrist W., Drozdz R., Et al., The receptor for α-melanotropin of mouse and human melanoma cells. Application of a potent α-melanotropin photoaffinity label, J Biol Chem, 264, pp. 14277-14281, (1989)

[9]

Tatro J.B., Entwistle M.L., Lester B.R., Et al., Melanotropic receptors of murine melanoma characterized in cultured cells and demonstrated in experimental tumours in situ, Cancer Res, 50, pp. 1237-1242, (1990)

[10]

Kreiner P.W., Gold C.J., Keirns J.J., Et al., MSH-sensitive adenyl cyclase in the Cloudman melanoma, Yale J Biol Med, 46, pp. 583-591, (1973)

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