Beta 2-microglobulin regulates amyloid precursor-like protein 2 expression and the migration of pancreatic cancer cells

Bailee H. Sliker, Benjamin T. Goetz, Haley L. Peters, Brittany J. Poelaert, Gloria E.O. Borgstahl, Joyce C. Solheim

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Beta 2-microglobulin (β 2 m) is a component of the major histocompatibility complex (MHC) class I molecule, which presents tumor antigens to T lymphocytes to trigger cancer cell destruction. Notably, β 2 m has been reported as persistently expressed, rather than down regulated, in some tumor types. For renal cell and oral squamous cell carcinomas, β 2 m expression has been linked to increased migratory capabilities. The migratory ability of pancreatic cancer cells contributes to their metastatic tendencies and lethal nature. Therefore, in this study, we examined the impact of β 2 m on pancreatic cancer cell migration. We found that β 2 m protein is amply expressed in several human pancreatic cancer cell lines (S2-013, PANC-1, and MIA PaCa-2). Reducing β 2 m expression by short interfering RNA (siRNA) transfection significantly slowed the migration of the PANC-1 and S2-013 cancer cell lines, but increased the migration of the MIA PaCa-2 cell line. The amyloid precursor-like protein 2 (APLP2) has been documented as contributing to pancreatic cancer cell migration, invasiveness, and metastasis. We have previously shown that β 2 m/HLA class I/peptide complexes associate with APLP2 in S2-013 cells, and in this study we also detected their association in PANC-1 cells but not MIA PaCa-2 cells. In addition, siRNA down regulation of β 2 m expression diminished the expression of APLP2 in S2-013 and PANC-1 but heightened the level of APLP2 in MIA PaCa-2 cells, consistent with our migration data and co-immunoprecipitation data. Thus, our findings indicate that β 2 m regulates pancreatic cancer cell migration, and furthermore suggest that APLP2 is an intermediary in this process.

Original languageEnglish (US)
Pages (from-to)931-940
Number of pages10
JournalCancer Biology and Therapy
Volume20
Issue number6
DOIs
StatePublished - Jun 3 2019

Keywords

  • Amyloid precursor-like protein 2
  • HLA class I molecule
  • beta 2-microglobulin
  • migration
  • pancreatic cancer

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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