Department of Hematology/Oncology, Gundersen Medical Foundation, La Crosse, WI 54601, USA.
Int J Cancer. 2013 Apr 15;132(8):1761-70. doi: 10.1002/ijc.27873. Epub 2012 Oct 29.
CD43 is a transmembrane sialoglycoprotein. Normally the molecule is only produced by white blood cells where it regulates functions such as intercellular adhesion, intracellular signaling, apoptosis, migration and proliferation. Two CD43 antibodies were used to interrogate 66 cases of non-small cell lung cancer (NSCLC) and 24 cases of small cell lung cancer (SCLC). In addition, we engineered the CD43-positive lung cancer cell line A549 to stably express either non-targeted or CD43-targeted small-interfering RNA (siRNA). These lines were then subjected to in vitro assays of apoptosis, natural killer (NK) cell cytotoxicity, intercellular adhesion and transendothelial migration. A xenograft mouse model evaluated the ability of the lines to grow primary tumors in vivo. CD43 was found to be expressed in the majority of both SCLC and NSCLC. Inclusive of CD43-negative tumors, differential patterns of nuclear and cytoplasmic expression of CD43 define four molecular subcategories of lung cancer. Targeting CD43 in A549 lung cancer cells, increased homotypic adhesion, decreased heterotypic adhesion and transendothelial migration, increased susceptibility to apoptosis and increased vulnerability to lysis by NK cells. Furthermore, targeting inhibited the growth of primary tumors in nude mice.
CD43 是一种跨膜唾液酸糖蛋白。正常情况下，该分子仅由白细胞产生，在白细胞中它调节细胞间黏附、细胞内信号转导、细胞凋亡、迁移和增殖等功能。我们使用两种 CD43 抗体检测了 66 例非小细胞肺癌（NSCLC）和 24 例小细胞肺癌（SCLC）。此外，我们将 CD43 阳性肺癌细胞系 A549 进行基因工程改造，使其稳定表达非靶向或 CD43 靶向的小干扰 RNA（siRNA）。然后对这些细胞系进行体外细胞凋亡、自然杀伤（NK）细胞细胞毒性、细胞间黏附和跨内皮迁移的检测。在异种移植小鼠模型中评估这些细胞系在体内形成原发性肿瘤的能力。我们发现 CD43 在大多数 SCLC 和 NSCLC 中均有表达。包括 CD43 阴性肿瘤在内，CD43 的核和细胞质表达的差异模式定义了肺癌的四个分子亚型。在 A549 肺癌细胞中靶向 CD43，可增加同质黏附、减少异质黏附和跨内皮迁移，增加对细胞凋亡的敏感性，并增加对 NK 细胞裂解的易感性。此外，靶向治疗抑制了裸鼠原发性肿瘤的生长。
