Nagahama M, Funasaka Y, Fernandez-Frez M L, Ohashi A, Chakraborty A K, Ueda M, Ichihashi M
Department of Dermatology, Kobe University School of Medicine, Japan.
Br J Dermatol. 1998 Jun;138(6):981-5. doi: 10.1046/j.1365-2133.1998.02263.x.
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.
据报道，促黑素（MSH）可增强小鼠模型中黑色素瘤细胞的实验性转移行为。在培养的正常人黑素细胞和转移性黑色素瘤中已检测到α-MSH的产生以及MSH受体（黑皮质素1受体基因）的表达。然而，MSH在人黑色素瘤细胞转移行为中的确切作用尚不清楚。为了阐明源自阿片促黑素皮质激素原（POMC）的肽（包括α-MSH）在黑色素瘤发生和发展中的可能作用，我们采用免疫组织化学方法分析了α-MSH、促肾上腺皮质激素（ACTH）和β-内啡肽在各种良性色素性痣细胞病变和恶性黑色素瘤中的定位。21例普通痣和发育异常痣样本中有3例在痣细胞中显示可检测到的α-MSH染色，15例样本中有5例和6例分别对ACTH和β-内啡肽染色呈弱阳性。在黑色素瘤样本中，45例中有24例、39例中有23例、42例中有30例分别显示用α-MSH、ACTH和β-内啡肽抗体染色呈阳性。此外，与痣相比，在结节性黑色素瘤、垂直生长的肢端雀斑样痣黑色素瘤、浅表扩散性黑色素瘤以及转移灶样本中，所有三种抗体的染色均更强烈且弥漫。尽管晚期黑色素瘤细胞中这种对源自POMC的肽的强染色是否表明自分泌或旁分泌调节的作用尚待确定，但我们的结果提示POMC基因产物可能参与黑色素瘤的进展。
