Tsukamoto H, Mishima Y, Hayashibe K, Sasase A
Department of Dermatology, Kobe University School of Medicine, Japan.
J Invest Dermatol. 1992 Jan;98(1):116-20. doi: 10.1111/1523-1747.ep12496020.
We examined the altered expression of alpha-smooth muscle actin (alpha-Sm) in human benign, pre-malignant, and malignant pigment cell tumors by immunohistochemical as well as biochemical (Western blot) analysis using anti-alpha-Sm monoclonal antibody (anti-alpha-Sm MoAb). The expression of alpha-Sm has been revealed immunohistochemically to be associated with mesodermal cells rather than with pigment cells. Western blot analysis using anti-alpha-Sm MoAb detected alpha-Sm expression as a 43-kD band in the extracts from normal papillary dermis, nevus cell nevus, and metastatic melanoma with stromal tissues, but not from primary melanoma with stromal tissues examined. The above findings of alpha-Sm expression by Western blot analysis were further characterized immunohistochemically in terms of the localization at the cellular level as follows. 1) In normal papillary dermis, pericytes encircling capillary vessels showed only positive staining with anti-alpha-Sm MoAb. 2) In nevus tissues, nevus cells were not shown to be positively stained, despite similar positivity of pericytes in normal papillary dermis. 3) In melanoma tissues, alpha-Sm expression of metastatic melanoma detected by Western blot analysis was found to be derived from fibroblasts with smooth-muscle differentiation (myofibroblasts), but not from melanoma cells. Such myofibroblastic stromal changes could not be found on primary melanoma tissue sections, which showed no reactivity in Western blot analysis. We conclude that the major sources of alpha-Sm in benign and pre-malignant pigment cell tumors are capillary pericytes, whereas alpha-Sm found in malignant melanoma tissue is primarily from melanoma-surrounding stromal fibroblasts that were changed to myofibroblasts by some cytokine factor(s), presumably secreted from melanoma cells.
我们使用抗α-平滑肌肌动蛋白单克隆抗体（抗α-Sm MoAb），通过免疫组织化学以及生化（蛋白质印迹法）分析，检测了α-平滑肌肌动蛋白（α-Sm）在人类良性、癌前和恶性色素细胞肿瘤中的表达变化。免疫组织化学显示，α-Sm的表达与中胚层细胞相关，而非色素细胞。使用抗α-Sm MoAb进行的蛋白质印迹分析在正常乳头真皮、痣细胞痣以及伴有基质组织的转移性黑色素瘤提取物中检测到α-Sm表达为一条43-kD条带，但在所检测的伴有基质组织的原发性黑色素瘤提取物中未检测到。蛋白质印迹分析得出的上述α-Sm表达结果，通过免疫组织化学在细胞水平定位方面进一步得到如下表征。1）在正常乳头真皮中，环绕毛细血管的周细胞仅显示抗α-Sm MoAb阳性染色。2）在痣组织中，尽管正常乳头真皮中的周细胞呈相似阳性，但痣细胞未显示阳性染色。3）在黑色素瘤组织中，蛋白质印迹分析检测到的转移性黑色素瘤的α-Sm表达源自具有平滑肌分化的成纤维细胞（肌成纤维细胞），而非黑色素瘤细胞。在原发性黑色素瘤组织切片上未发现这种肌成纤维细胞性基质变化，其在蛋白质印迹分析中无反应性。我们得出结论，良性和癌前色素细胞肿瘤中α-Sm的主要来源是毛细血管周细胞，而恶性黑色素瘤组织中发现的α-Sm主要源自黑色素瘤周围的基质成纤维细胞，这些成纤维细胞因一些可能由黑色素瘤细胞分泌的细胞因子而转变为肌成纤维细胞。
