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Exp Cell Res ; 390(2): 111960, 2020 05 15.
Article in English | MEDLINE | ID: mdl-32194036

ABSTRACT

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.


Subject(s)
Cell Movement/genetics , Gene Expression Regulation, Neoplastic , HLA-B Antigens/genetics , Integrin beta1/genetics , Pancreas/metabolism , Cell Line, Tumor , Cell Proliferation , Focal Adhesion Kinase 1/genetics , Focal Adhesion Kinase 1/metabolism , HLA-B Antigens/metabolism , Humans , Integrin alpha2/genetics , Integrin alpha2/metabolism , Integrin beta1/metabolism , Organ Specificity , Pancreas/pathology , Protein Isoforms/antagonists & inhibitors , Protein Isoforms/genetics , Protein Isoforms/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Signal Transduction
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