Department of Regulation Biochemistry, Kitasato University School of Allied Sciences Sagamihara, Japan.
Cancer Med. 2012 Aug;1(1):39-46. doi: 10.1002/cam4.12. Epub 2012 Jul 13.
The concept of "lymphangiosarcoma" remains obscure. Therefore, we reported a patient with lymphangiosarcoma, resistant to immunotherapy. The patient presented with impressive and discriminative features: clinically an ill-defined edematous lesion with lymphorrhea and pathologically atypical vascular channel formation without extravasation of blood, clearly distinguished from common angiosarcoma with hemorrhage. From this case, a lymphangiosarcoma cell line, MO-LAS, was established and its characteristics were compared with the hemangiosarcoma cell line, ISO-HAS. Flow cytometric analysis revealed that MO-LAS was negative for factor VIII-related antigen, but positive for CD31, D2-40, NZ-1, and vascular endothelial growth factor receptor-3 (VEGFR-3), similar to ISO-HAS. However, MO-LAS expressed a much higher level of homeobox gene PROX1, indicating a lymphatic phenotype, compared with ISO-HAS. Furthermore, MO-LAS showed a much lesser expression of oncogenes and much lower sensitivity against lymphokine-activated killer (LAK) cells. Lymphangiosarcoma may be difficult to recognize by the immune system. Conclusively, the establishment of MO-LAS, a novel angiosarcoma cell line bearing lymphatic characters, strongly suggests the entity of lymphangiosarcoma.
“淋巴管肉瘤”的概念仍然模糊不清。因此,我们报告了一例对免疫治疗有耐药性的淋巴管肉瘤患者。该患者具有明显而独特的特征:临床上表现为界限不清的水肿性病变,伴有淋巴液渗出,病理上表现为非典型的血管通道形成,无血液外渗,明显区别于常见的伴有出血的血管肉瘤。从该病例中建立了淋巴管肉瘤细胞系 MO-LAS,并将其特征与血管肉瘤细胞系 ISO-HAS 进行了比较。流式细胞术分析显示,MO-LAS 阴性表达第八因子相关抗原,但阳性表达 CD31、D2-40、NZ-1 和血管内皮生长因子受体-3(VEGFR-3),与 ISO-HAS 相似。然而,与 ISO-HAS 相比,MO-LAS 表达更高水平的同源盒基因 PROX1,表明具有淋巴管表型。此外,MO-LAS 表达的癌基因较少,对淋巴因子激活的杀伤(LAK)细胞的敏感性也较低。淋巴管肉瘤可能难以被免疫系统识别。综上所述,MO-LAS 的建立,一种具有淋巴管特征的新型血管肉瘤细胞系,强烈提示了淋巴管肉瘤的实体存在。