Integrin alpha 2 is associated with tumor progression and postoperative recurrence in non-small cell lung cancer

Integrin alpha 2 is associated with tumor progression and postoperative recurrence in non-small cell lung cancer
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DOI:
10.1093/jjco/hyac148
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发表时间:
2022-09-23
影响因子:
2.4
通讯作者:
Nagase, Takahide
Nagase, Takahide
中科院分区:
医学4区
文献类型:
--
作者:
Matsumoto, Yoko;Kage, Hidenori;Nagase, Takahide

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背景整合素是一种跨膜蛋白,介导细胞与细胞外基质的黏附。尽管整合素α2的表达与多种肿瘤的转移、侵袭性和细胞分化有关,但整合素α2在肺癌中的作用尚未得到详细研究。这项研究的目的是确定非小细胞肺癌中整合素α2的异常表达是否以及如何导致不同的结果。方法采用定量聚合酶链式反应检测100例手术切除的非小细胞肺癌组织中整合素α2的表达。我们将患者分为高表达组和低表达组,并分析了存活率。对人肺癌细胞系的细胞形态、黏附、增殖、迁移和侵袭进行了观察。结果100例中女性41例,中位年龄71岁。非小细胞肺癌中整合素α2的高表达与无复发生存率降低有关(P=0.004)。H522细胞株中整合素α2的过表达对细胞的增殖和侵袭没有影响,但可增加细胞体积(H522细胞1416um(2)vs470um(2),P<0.001;H661细胞1822um(2)vs1029um(2,P=0.02))、黏附(H522和H661细胞0.001)和迁移(H522细胞缝隙填充面积71%vs36%,P<0.001;H661细胞57%vs26%,P=0.001)。结论整合素α2在肺癌的黏附和转移中可能起重要作用,并可能导致较高的复发风险,非小细胞肺癌中整合素α2的高表达与术后复发有关。整合素α2在肿瘤的黏附和转移中起着重要作用,这可能导致更高的复发风险。
Background Integrins are transmembrane proteins that mediate cell adhesion to extracellular matrix. Whereas expression of integrin alpha 2 is associated with motility, invasiveness and cellular differentiation in various tumors, the role of integrin alpha 2 in lung cancer has not been studied in detail. The aim of this study was to determine whether and how aberrant integrin alpha 2 expression in non-small cell lung cancer leads to different outcomes. Methods We measured expression of integrin alpha 2 by quantitative polymerase chain reaction in 100 samples collected from non-small cell lung cancer patients who had undergone surgical resection. We assigned patients to high and low expression groups and analyzed survival. Cellular morphology, adhesion, proliferation, migration and invasion were examined in human lung cancer cell lines. Results Among 100 cases, 41 were female, with a median age of 71 years. High expression of integrin alpha 2 in non-small cell lung cancer was associated with lower recurrence-free survival (P = 0.004). Overexpression of integrin alpha 2 in cell lines had no effect on cell proliferation or invasion but resulted in increased cell size (1416 mu m(2) versus 470 mu m(2) in H522 cells, P < 0.001; 1822 mu m(2) versus 1029 mu m(2) in H661 cells, P = 0.02), adhesion (P < 0.001 in H522 and H661 cells) and migration (gap area filled was 71% versus 36% in H522 cells, P < 0.001; 57% versus 26% in H661 cells, P = 0.001). These changes were suppressed by E7820, an inhibitor of integrin alpha 2. Conclusions Integrin alpha 2 may play a significant role in lung cancer adhesion and migration, and may lead to a higher risk of recurrence.High expression of integrin alpha 2 in non-small cell lung cancer was associated with postoperative recurrence. Integrin alpha 2 plays a significant role in cancer adhesion and migration, which may lead to a higher risk of recurrence.