Potent phagocytic activity discriminates metastatic and primary human malignant melanomas: A key role of ezrin
Potent phagocytic activity discriminates metastatic and primary human malignant melanomas: A key role of ezrin
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DOI：
10.1097/01.lab.0000098425.03006.42
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发表时间：
2003-11-01
影响因子：
5
通讯作者：
Fais, S
中科院分区：
文献类型：
--
作者：
Lugini, L;Lozupone, F;Fais, S
在人类肿瘤中已经观察到吞噬的特征，但肿瘤细胞的吞噬器官和这种现象的机制尚未明确。为了研究吞噬现象、其潜在机制及其在肿瘤生物学中的可能作用，我们使用人类黑色素瘤细胞作为原型模型。我们的研究结果表明，人黑色素瘤在体内发生了凋亡细胞的吞噬过程。这一发现与人类黑色素瘤细胞在体外表达所有已知的溶酶体和吞噬标志物在其细胞质囊泡上的证据是一致的，并且吞噬过程发生在这些囊泡中。然而，来自转移性病变的人类黑色素瘤细胞具有有效的吞噬机制，对不同来源的乳胶珠、酵母和凋亡细胞具有巨噬细胞样活性，这与人类原代巨噬细胞相当。此外，肌动蛋白结合蛋白ezrin在黑色素瘤细胞和人腺癌衍生细胞的吞噬空泡上表达；细胞松弛素B治疗和ezrin合成特异性抑制均强烈影响黑色素瘤细胞的吞噬活性。这表明与肌动蛋白细胞骨架的关联是这种现象发展的关键要求。因此，我们的数据为转移性黑色素瘤细胞发挥的强大吞噬活性提供了证据，这可能与决定人类黑色素瘤的侵袭性水平有关。这表明，吞噬活性的评估可作为评估人类黑色素瘤恶性程度的新工具。此外，我们的数据表明，旨在抑制肌动蛋白组装到吞噬体膜的基因治疗或药物治疗可能被提出作为控制肿瘤侵袭性的新策略。
Features of phagocytosis have been observed in human tumors, but the phagocytic apparatus of tumor cells and the mechanism(s) underlying this phenomenon have yet to be defined. To address the phenomenon of phagocytosis, its underlying mechanism(s), and its possible role in tumor biology, we used human melanoma cells as a prototypic model. Our results showed that a process of phagocytosis of apoptotic cells occurs in vivo in human melanoma. This finding was consistent with evidence that human melanoma cells in vitro express all of the known lysosomal and phagocytic markers on their cytoplasmic vesicles and that a process of phagocytosis occurs in these vesicles. However, exclusively human melanoma cells deriving from metastatic lesions possess an efficient phagocytic machinery responsible for a macrophage-like activity against latex beads, yeast, and apoptotic cells of different origins, which was comparable to that of human primary macrophages. Moreover, the actin-binding protein ezrin was expressed on phagocytic vacuoles of melanoma cells and of cells deriving from a human adenocarcinoma; both treatment with cytochalasin B and specific inhibition of ezrin synthesis strongly affected the phagocytic activity of melanoma cells. This suggests that the association with the actin cytoskeleton is a crucial requirement for the development of this phenomenon. Hence our data provide evidence for a potent phagocytic activity exerted by metastatic melanoma cells possibly involved in determining the level of aggressiveness of human melanoma. This suggests that the assessment of phagocytic activity may be exploited as a new tool to evaluate the malignancy of human melanoma. Moreover, our data suggest that gene therapy or drug treatments aimed at inhibiting actin assembly to the phagosomal membranes may be proposed as a new strategy for the control of tumor aggressiveness.