Rouleau Cecile, Curiel Maritza, Weber William, Smale Robert, Kurtzberg Leslie, Mascarello James, Berger Carol, Wallar Gina, Bagley Rebecca, Honma Nakayuki, Hasegawa Kazumasa, Ishida Isao, Kataoka Shiro, Thurberg Beth L, Mehraein Khodadad, Horten Bruce, Miller Glenn, Teicher Beverly A
Genzyme Corporation, Framingham, Massachusetts 01701, USA.
Clin Cancer Res. 2008 Nov 15;14(22):7223-36. doi: 10.1158/1078-0432.CCR-08-0499.
Endosialin/CD248/tumor endothelial marker 1 is expressed in stromal cells, endothelial cells, and pericytes in various tumors; however, few studies have focused on expression in malignant cells.
We studied expression of endosialin in clinical specimens, cell culture, and animal models and designed an anti-endosialin therapeutic prototype.
Fifty human tumor cell lines and 6 normal cell types in culture were assayed by reverse transcription-PCR and/or flow cytometry for endosialin. Cell surface protein was found on 7 sarcoma lines, 1 neuroblastoma, and 4 normal cell types in culture. A fully human anti-endosialin antibody bound to human A-673 Ewing's sarcoma cells and SK-N-AS neuroblastoma cells but not HT-1080 cells. Exposure of cells to an anti-human IgG conjugated to saporin resulted in growth inhibition only of endosialin-expressing cells. Endosialin expression was assessed by immunohistochemistry in 250 clinical specimens of human cancer including 20 cancer subtypes. Endosialin is frequently found in human cancers. Endosialin expression is mainly a perivascular feature in carcinomas, with some expression in stromal cells. In sarcomas, endosialin is expressed by malignant cells, perivascular cells, and stromal cells. Development and characterization of experimental models for studying endosialin biology in sarcomas and evaluating anti-endosialin therapies is presented.
Findings suggest that an anti-endosialin immunotoxin might be a promising therapeutic approach for endosialin-positive neoplasia, especially synovial sarcoma, fibrosarcoma, malignant fibrous histiocytoma, liposarcoma, and osteosarcoma. Thus, a diagnostic/therapeutic targeted therapeutic approach to treatment of endosialin-expressing tumors may be possible.
内唾液酸酶/CD248/肿瘤内皮标志物1在多种肿瘤的基质细胞、内皮细胞和周细胞中表达；然而，很少有研究关注其在恶性细胞中的表达。
我们研究了内唾液酸酶在临床标本、细胞培养和动物模型中的表达，并设计了一种抗内唾液酸酶治疗原型。
通过逆转录-聚合酶链反应和/或流式细胞术检测了50种人肿瘤细胞系和6种培养的正常细胞类型中的内唾液酸酶。在7种肉瘤细胞系、1种神经母细胞瘤和4种培养的正常细胞类型中发现了细胞表面蛋白。一种完全人源化抗内唾液酸酶抗体与人类A-673尤文肉瘤细胞和SK-N-AS神经母细胞瘤细胞结合，但不与HT-1080细胞结合。将细胞暴露于与皂草素偶联的抗人IgG中，仅导致表达内唾液酸酶的细胞生长受到抑制。通过免疫组织化学评估了250份包括20种癌症亚型的人类癌症临床标本中的内唾液酸酶表达。内唾液酸酶在人类癌症中经常被发现。在癌中，内唾液酸酶表达主要是血管周围特征，在基质细胞中有一些表达。在肉瘤中，内唾液酸酶由恶性细胞、血管周围细胞和基质细胞表达。本文介绍了用于研究肉瘤中内唾液酸酶生物学和评估抗内唾液酸酶疗法的实验模型的建立和特征。
研究结果表明，抗内唾液酸酶免疫毒素可能是治疗内唾液酸酶阳性肿瘤，尤其是滑膜肉瘤、纤维肉瘤、恶性纤维组织细胞瘤、脂肪肉瘤和骨肉瘤的一种有前景的治疗方法。因此，针对表达内唾液酸酶的肿瘤的诊断/治疗靶向治疗方法可能是可行的。
