Hebei Bone Research Institute, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China.
PLoS One. 2013 Aug 5;8(8):e70689. doi: 10.1371/journal.pone.0070689. Print 2013.
B7-H3 is a member of the B7-family of co-stimulatory molecules, which has been shown to be broadly expressed in various tumor tissues, and which plays an important role in adaptive immune responses. The role of B7-H3 in osteosarcoma, however, remains unknown. In this study we used immunohistochemistry to analyze B7-H3 expression in 61 primary osteosarcoma tissues with case-matched adjacent normal tissues, and 37 osteochondroma and 20 bone fibrous dysplasia tissues. B7-H3 expression was expressed in 91.8% (56/61) of the osteosarcoma lesions, and the intensity of B7-H3 expression in osteosarcoma was significantly increased compared with adjacent normal tissues, osteochondroma and bone fibrous dysplasia tissues (p<0.001). Patients with high tumor B7-H3 levels had a significantly shorter survival time and recurrence time than patients with low tumor B7-H3 levels (p<0.001). Moreover, tumor B7-H3 expression inversely correlated with the number of tumor-infiltrating CD8(+) T cells (p<0.05). In vitro, increasing expression of B7-H3 promotes osteosarcoma cell invasion, at least in part by upregulating matrix metalloproteinase-2 (MMP-2). In conclusion, our study provides the first evidence of B7-H3 expression in osteosarcoma cells as a potential mechanism controlling tumor immunity and invasive malignancy, and which is correlated with patients' survival and metastasis.
B7-H3 是 B7 家族共刺激分子的成员,已被证明在各种肿瘤组织中广泛表达,在适应性免疫反应中发挥重要作用。然而,B7-H3 在骨肉瘤中的作用尚不清楚。在这项研究中,我们使用免疫组织化学方法分析了 61 例原发性骨肉瘤组织和配对的相邻正常组织、37 例骨软骨瘤和 20 例骨纤维结构不良组织中的 B7-H3 表达。B7-H3 在 91.8%(56/61)的骨肉瘤病变中表达,与相邻正常组织、骨软骨瘤和骨纤维结构不良组织相比,骨肉瘤中 B7-H3 的表达强度显著增加(p<0.001)。B7-H3 高表达的肿瘤患者的生存时间和复发时间明显短于 B7-H3 低表达的肿瘤患者(p<0.001)。此外,肿瘤 B7-H3 表达与肿瘤浸润 CD8(+)T 细胞的数量呈负相关(p<0.05)。体外实验表明,B7-H3 表达的增加促进骨肉瘤细胞的侵袭,至少部分是通过上调基质金属蛋白酶-2(MMP-2)实现的。综上所述,我们的研究首次提供了证据表明 B7-H3 在骨肉瘤细胞中的表达是一种潜在的控制肿瘤免疫和侵袭性恶性的机制,与患者的生存和转移相关。