Simonart T, Degraef C, Mosselmans R, Hermans P, Lunardi-Iskandar Y, Noel J C, Van Vooren J P, Parent D, Heenen M, Galand P
Department of Dermatology, Erasme University Hospital, Brussels, Belgium.
J Invest Dermatol. 2001 May;116(5):679-85. doi: 10.1046/j.1523-1747.2001.01319.x.
Whether Kaposi's sarcoma is a true neoplasm or a reactive endothelial cell outgrowth triggered by inflammatory cytokines remains unclear. In this study, we investigated the differential invasive properties of activated endothelial cells and Kaposi's sarcoma cells in a model of de-epidermized dermis, supplying the cells with matrix barriers similar to those found in vivo. Cells derived from early "patch-stage" and from late "nodular-stage" Kaposi's sarcoma lesions exhibited similar invasive properties, which indicates that cells with an invasive potential are present in the early stages of tumor development. Slow accumulation of the cells into the extracellular matrix, together with a low proliferation index and with expression of anti-apoptotic proteins, suggest that the progression of Kaposi's sarcoma may be related to escape from cell death rather than to increased proliferation. The Kaposi's sarcoma-Y1 cell line, which is tumorigenic in nude mice, also exhibited invasive properties. By contrast to the Kaposi's sarcoma-derived spindle cells, however, which were scattered between the collagen bundles, the Kaposi's sarcoma-Y1 cell population had a higher proliferation index and displayed a multilayer arrangement. Inflammatory cytokines and Kaposi's sarcoma cell supernatant could activate and stimulate the growth of human dermal microvascular endothelial cell, but could not induce their invasion in this model, showing that activated endothelial cells do not fit all the requirements to traverse the various barriers found in the dermal extracellular matrix. These results confer to Kaposi's sarcoma cells a tumor phenotype and suggest that the in vivo dominant endothelial cell population represents a reactive hyperplasia rather than the true tumor process.
卡波西肉瘤究竟是一种真正的肿瘤，还是由炎性细胞因子触发的反应性内皮细胞增生，目前尚不清楚。在本研究中，我们在去表皮真皮模型中研究了活化内皮细胞和卡波西肉瘤细胞的不同侵袭特性，为细胞提供类似于体内发现的基质屏障。来自早期“斑块期”和晚期“结节期”卡波西肉瘤病变的细胞表现出相似的侵袭特性，这表明具有侵袭潜能的细胞在肿瘤发展的早期阶段就已存在。细胞缓慢积聚到细胞外基质中，同时增殖指数较低且抗凋亡蛋白表达，提示卡波西肉瘤的进展可能与逃避细胞死亡有关，而非增殖增加。在裸鼠中具有致瘤性的卡波西肉瘤 - Y1细胞系也表现出侵袭特性。然而，与散布在胶原束之间的卡波西肉瘤来源的梭形细胞不同，卡波西肉瘤 - Y1细胞群体具有更高的增殖指数并呈现多层排列。炎性细胞因子和卡波西肉瘤细胞上清液可激活并刺激人真皮微血管内皮细胞的生长，但在该模型中不能诱导其侵袭，这表明活化的内皮细胞并不完全符合穿越真皮细胞外基质中各种屏障的所有要求。这些结果赋予卡波西肉瘤细胞肿瘤表型，并提示体内占主导地位的内皮细胞群体代表反应性增生而非真正的肿瘤过程。
