Department of Urology, University of Tuebingen Hospital, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany.
Center for Medical Research, University of Tuebingen Hospital, Waldhoernlestr. 22, 72072 Tuebingen, Germany.
Int J Mol Sci. 2022 Apr 29;23(9):4969. doi: 10.3390/ijms23094969.
The cell surface molecule CD276 (B7-H3) is an immune checkpoint antigen. The elevated expression of CD276 on tumors contributes to the suppression of anti-tumor T-cell responses and correlates with poor prognosis.
The expression of CD276 was explored in vitro on eight urothelial carcinoma cell lines (UM-UC) in comparison to eight normal urothelial cells (NUCs) by RT-qPCR, Western blotting, and flow cytometry. Cell proliferation was enumerated over consecutive passages. The expression of cancer stem cell markers CD24 and CD44, cytokeratins, and vimentin was investigated by immunofluorescence. The expression of CD276 in bladder tumor samples and metastases was explored by immunohistochemistry.
Expression of CD276 on cell surfaces was elevated on UM-UCs when compared to NUCs. In UM-UCs, CD276 transcripts correlated moderately positive with CD276 protein expression (ρ = 0.660) and strongly positive with CD276 surface-expression (ρ = 0.810). CD276 mRNA expression (ρ = -0.475) and CD276 protein expression (ρ = -0.417) had a significant negative correlation with proliferation, while a significant correlation between proliferation and cell surface expression was not observed in UM-UCs.
The expression of CD276 on UM-UC bladder tumor cell surfaces is elevated. Slow proliferating UM-UC cells express more CD276 mRNA and protein than fast proliferating cells. In patients, slow proliferating CD276 tumor (stem) cells may evade immune surveillance. However, cancer therapy targeting CD276 may be effective in the treatment of slow proliferating tumor cells.
细胞表面分子 CD276（B7-H3）是一种免疫检查点抗原。肿瘤中 CD276 的高表达有助于抑制抗肿瘤 T 细胞反应，并与预后不良相关。
通过 RT-qPCR、Western blot 和流式细胞术，在 8 种尿路上皮癌细胞系（UM-UC）与 8 种正常尿路上皮细胞（NUC）中研究 CD276 的表达。通过连续传代计数细胞增殖。通过免疫荧光法研究癌症干细胞标志物 CD24 和 CD44、细胞角蛋白和波形蛋白的表达。通过免疫组织化学法研究膀胱肿瘤样本和转移灶中 CD276 的表达。
与 NUCs 相比，UM-UC 细胞表面 CD276 的表达升高。在 UM-UC 中，CD276 转录物与 CD276 蛋白表达呈中度正相关（ρ=0.660），与 CD276 表面表达呈强正相关（ρ=0.810）。CD276 mRNA 表达（ρ=-0.475）和 CD276 蛋白表达（ρ=-0.417）与增殖呈显著负相关，而在 UM-UC 中未观察到增殖与细胞表面表达之间的显著相关性。
UM-UC 膀胱肿瘤细胞表面 CD276 的表达升高。增殖缓慢的 UM-UC 细胞比增殖快速的细胞表达更多的 CD276 mRNA 和蛋白。在患者中，增殖缓慢的 CD276 肿瘤（干细胞）细胞可能逃避免疫监视。然而，针对 CD276 的癌症治疗可能对治疗增殖缓慢的肿瘤细胞有效。
