Eppley Institute for Research in Cancer and Allied Diseases and the Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
Columbia University Department of Medicine and the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA.
Exp Cell Res. 2020 May 15;390(2):111960. doi: 10.1016/j.yexcr.2020.111960. Epub 2020 Mar 16.
Human leukocyte antigen (HLA) class I molecules present antigenic peptides to cytotoxic T cells, causing lysis of malignant cells. Transplantation biology studies have implicated HLA class I molecules in cell migration, but there has been little evidence presented that they influence cancer cell migration, a contributing factor in metastasis. In this study, we examined the effect of HLA-B on pancreatic cancer cell migration. HLA-B siRNA transfection increased the migration of the S2-013 pancreatic cancer cells but, in contrast, reduced migration of the PANC-1 and MIA PaCa-2 pancreatic cancer cell lines. Integrin molecules have previously been implicated in the upregulation of pancreatic cancer cell migration, and knockdown of HLA-B in S2-013 cells heightened the expression of integrin beta 1 (ITGB1), but in the PANC-1 and MIA PaCa-2 cells HLA-B knockdown diminished ITGB1 expression. A transmembrane sequence in an S2-013 HLA-B heavy chain matches a corresponding sequence in HLA-B in the BxPC-3 pancreatic cancer cell line, and knockdown of BxPC-3 HLA-B mimics the effect of S2-013 HLA-B knockdown on migration. In total, our findings indicate that HLA-B influences the expression of ITGB1 in pancreatic cancer cells, with concurrent distinctions in transmembrane sequences and effects on the migration of the cells.
人类白细胞抗原(HLA)I 类分子将抗原肽呈递给细胞毒性 T 细胞,导致恶性细胞溶解。移植生物学研究表明 HLA I 类分子参与细胞迁移,但很少有证据表明它们会影响癌细胞迁移,这是转移的一个促成因素。在这项研究中,我们研究了 HLA-B 对胰腺癌细胞迁移的影响。HLA-B siRNA 转染增加了 S2-013 胰腺癌细胞的迁移,但相反,降低了 PANC-1 和 MIA PaCa-2 胰腺癌细胞系的迁移。整合素分子先前被认为参与上调胰腺癌细胞迁移,而 S2-013 细胞中 HLA-B 的敲低增加了整合素 beta 1(ITGB1)的表达,但在 PANC-1 和 MIA PaCa-2 细胞中,HLA-B 的敲低减少了 ITGB1 的表达。S2-013 HLA-B 重链中的跨膜序列与 BxPC-3 胰腺癌细胞系中的 HLA-B 相应序列匹配,而 BxPC-3 HLA-B 的敲低模拟了 S2-013 HLA-B 敲低对迁移的影响。总的来说,我们的发现表明 HLA-B 影响胰腺癌细胞中 ITGB1 的表达,同时在跨膜序列和细胞迁移方面存在差异。