Simonart T, Degraef C, Noel J C, Fokan D, Zhou L, Pradier O, Ducarme M, Schandene L, Van Vooren J P, Parent D, Heenen M
Department of Dermatology, Erasme University Hospital, Brussels, Belgium.
J Invest Dermatol. 1998 Sep;111(3):349-53. doi: 10.1046/j.1523-1747.1998.00314.x.
The pathogenesis of Kaposi's sarcoma (KS), a tumor of probable vascular origin, remains an enigma. It is still unclear whether KS is a true malignancy or whether it represents a reactive polyclonal process. Using both an immunohistochemical and an immunoblot approach, we found that cells derived from KS lesions express significant levels of Bcl-2, a protein known to prolong cellular viability and to antagonize apoptosis. Bcl-2 expression was found in AIDS-related KS-derived cells, as well as in cells derived from iatrogenic and sporadic KS, indicating that Bcl-2 upregulation may be important in the pathogenesis of KS regardless of its epidemiologic form. By contrast, fibroblasts and dermal microvascular endothelial, cells which are the probable vascular progenitors of KS cells, expressed low levels of Bcl-2. The expression of Bcl-2 in KS-derived cells was associated with a long-term survival in serum-deprived conditions, a situation that has been shown to induce apoptosis in various cell types. Incubation of fibroblasts or of dermal microvascular endothelial cells with KS cell-free supernatants did not enhance Bcl-2 expression, suggesting that Bcl-2 expression is not mediated by an agent released by KS cells. Analogously, KS supernatants failed to promote the viability of fibroblasts and of dermal microvascular endothelial cells cultured in serum-free conditions. Our findings suggest that the spindle cells derived from KS have a survival advantage and may adequately represent the tumor cells of KS.
卡波西肉瘤（KS）是一种可能起源于血管的肿瘤，其发病机制仍是个谜。KS究竟是一种真正的恶性肿瘤，还是代表一种反应性多克隆过程，目前仍不清楚。通过免疫组织化学和免疫印迹方法，我们发现源自KS病变的细胞表达显著水平的Bcl-2，这是一种已知可延长细胞活力并拮抗细胞凋亡的蛋白质。在与艾滋病相关的KS衍生细胞以及医源性和散发性KS衍生细胞中均发现了Bcl-2表达，这表明无论其流行病学形式如何，Bcl-2上调在KS发病机制中可能都很重要。相比之下，成纤维细胞和真皮微血管内皮细胞（可能是KS细胞的血管前体细胞）表达的Bcl-2水平较低。KS衍生细胞中Bcl-2的表达与血清剥夺条件下的长期存活相关，血清剥夺已被证明可诱导多种细胞类型凋亡。用不含KS细胞的上清液培养成纤维细胞或真皮微血管内皮细胞，不会增强Bcl-2表达，这表明Bcl-2表达不是由KS细胞释放的因子介导的。类似地，KS上清液未能促进在无血清条件下培养的成纤维细胞和真皮微血管内皮细胞的活力。我们的研究结果表明，源自KS的梭形细胞具有生存优势，可能充分代表了KS的肿瘤细胞。
