TY - JOUR
T1 - Beta 2-microglobulin regulates amyloid precursor-like protein 2 expression and the migration of pancreatic cancer cells
AU - Sliker, Bailee H.
AU - Goetz, Benjamin T.
AU - Peters, Haley L.
AU - Poelaert, Brittany J.
AU - Borgstahl, Gloria E.O.
AU - Solheim, Joyce C.
N1 - Funding Information:
The authors thank Dr. Michael A. Hollingsworth and Dr. Michel Ouellette for providing cell lines, and thank Dr. Ted Hanson for donating antibodies used in this study. Support for this project was provided by the National Institutes of Health under Grant R21 CA223429 (to J.C.S.), the Pancreatic Cancer SPORE Grant P50 CA127297, the Fred & Pamela Buffett Cancer Center Support Grant P30 CA036727, the UNMC Eppley Structural Biology Facility, the Nebraska Center for Cellular Signaling COBRE Grant P20 GM103489, the Cancer Biology Training Program Grant T32 CA009476 (fellowships awarded to B.H.S. and H.L.P.), and by the UNMC Graduate Studies Office under the assistantship award program (to H.L.P. and B.P.).
Funding Information:
This work was supported by the National Institutes of Health [R21 CA223429]; National Institutes of Health [P50 CA127297]; National Institutes of Health [T32 CA009476]; National Institutes of Health [P20 GM103489]; National Institutes of Health [P30 CA036727]; UNMC Graduate Studies Office.
Publisher Copyright:
© 2019, © 2019 Taylor & Francis Group, LLC.
PY - 2019/6/3
Y1 - 2019/6/3
N2 - 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.
AB - 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.
KW - Amyloid precursor-like protein 2
KW - HLA class I molecule
KW - beta 2-microglobulin
KW - migration
KW - pancreatic cancer
UR - http://www.scopus.com/inward/record.url?scp=85062357090&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062357090&partnerID=8YFLogxK
U2 - 10.1080/15384047.2019.1580414
DO - 10.1080/15384047.2019.1580414
M3 - Article
C2 - 30810435
AN - SCOPUS:85062357090
SN - 1538-4047
VL - 20
SP - 931
EP - 940
JO - Cancer Biology and Therapy
JF - Cancer Biology and Therapy
IS - 6
ER -