Altered expression of alpha-smooth muscle actin (alpha-SMA) is known to indicate the morphological, tumorigenic and immunological changes occurring in tumour and stromal cells. The purpose of this study was to analyse the dynamics of alpha-SMA expression in human basal cell epithelioma (BCE) cells and their surrounding stromal cells, in the process of differentiation towards cutaneous appendages such as hair, sebaceous, apocrine and eccrine glands. Using anti-alpha-SMA specific monoclonal antibody (MAb), 17 of 36 BCEs (47%) were shown to express alpha-SMA, despite the usual absence of alpha-SMA in all eukaryotic cells except muscle cells. Solid, adenoid and sclerosing types of BCE expressed alpha-SMA more frequently, and in greater amount, than cystic, keratotic and superficial types. Furthermore, the expression of alpha-SMA in BCE cells significantly paralleled the expression of proliferating cell nuclear antigen (PCNA) in these cells. Thus, the altered expression of alpha-SMA may reflect the growing properties of BCE cells under the specific cellular regulations for differentiation. In addition, we have found anti-alpha-SMA MAb-positive fibroblasts with smooth muscle differentiation (myofibroblasts) in desmoplastic stroma surrounding BCE nests in 13 of 36 cases (36%). Coincidental expression of alpha-SMA in both BCE cells and stromal cells was found in nine of the 13 cases (69%), indicating the possibility of the induction of myofibroblastic stromal changes in surrounding tissues by cytokines secreted from BCE cells [e.g. basic fibroblast growth factor (bFGF)-like factor].
Distribution of HLA-DQA, -DQB and -DPB alleles in ninety-six Japanese patients with melanoma was analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and the association between clinical parameters and the presence of certain HLA class II alleles investigated. The frequency of HLA-DQB1*0302 was increased, while those of DQA1*0101(04), -DQA1*0401 and DRB1*0802 were decreased in melanoma patients compared with controls. Moreover, the frequency of HLA-DQA1*0103 in patients with acral lentiginous melanoma was increased compared with controls. However, none of these HLA class II alleles showed significant positive or negative associations after correction of the P value. In addition, there was no correlation between these antigens and clinical parameters. These results indicate that HLA class II alleles may not contribute to a strong susceptibility to melanoma in the Japanese.
White forelock and hypomelanotic macules of piebaldism have been revealed to have almost regularly distributed, dopa-positive melanocytes, though with lower density than normal, on separated epidermis despite previous reports describing few or no melanocytes in piebald spots. The melanocytes observed in piebald hypomelanotic spots seem to be classified into the following two types: (1) strongly dopa-positive and markedly hyperdendritic large cell type and (2) moderately dopa-positive and slightly hyperdendritic, oversized cell type. The former are primarily seen in hypomelanotic lesions, while the latter are seen in transitional lesions. The above difference seems to be associated with compensatory melanogenic function of melanocytes in vivo. Moreover, we have induced new hyperpigmented spots in hypomelanotic lesions, with the exception of white forelock, following therapy with oral methoxsalen plus ultraviolet A light.
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.
It has been shown that tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), stimulates the proliferation of normal human melanocytes, whereas it inhibits the growth of human melanoma cell lines. The expression of protein kinase C (PKC) subspecies, the major intracellular receptors for TPA, was examined in normal melanocytes and the four melanoma cell lines HM3KO, MeWo, HMV-1, and G361. PKC was partially purified and then separated into subspecies by column chromatography on Mono Q and hydroxyapatite successively, and finally subjected to immunoblot analysis using antibodies specific for the PKC subspecies. Of the PKC subspecies examined, delta-, epsilon-, and zeta-PKC were detected in both normal melanocytes and the four melanoma cell lines. In contrast, both alpha-PKC and beta-PKC were expressed in normal melanocytes, whereas either alpha-PKC or beta-PKC was detected in melanoma cells. Specifically, HM3KO, MeWo, and HMV-1 cells were shown to contain alpha-PKC but not beta-PKC, while G361 cells expressed beta-PKC but not alpha-PKC. The growth of these melanoma cells was suppressed by TPA treatment, and the growth of the G361 cells lacking alpha-PKC was inhibited more efficiently than the other melanoma cell lines which lacked beta-PKC. It was further shown that beta-PKC was not detected in freshly isolated human primary or metastatic melanoma tissues. These results suggest that the expression of alpha-PKC or beta-PKC may be altered during the malignant transformation of normal melanocytes and that loss of alpha-PKC or beta-PKC may be related to the inhibitory effect of TPA on the growth of melanoma cells.
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