Abstract B028: Beta 2-microglobulin promotes human pancreatic cancer cell migration

Abstract

Abstract Beta 2-microglublin (β2m) is a 12-kilodalton protein that serves as the non-covalently bound light chain in complex with the major histocompability complex (MHC) class I heavy chain. The human MHC class I heavy chain is known as human leukocyte antigen (HLA), which exists in three isotypes (HLA-A, -B, and -C). Much of the known function of β2m is in regards to its role in stabilizing the HLA class I heavy chain and thereby helping to present endogenous antigenic peptides to cytotoxic T cells. Notably, β2m has recently been found to be elevated in expression in a variety of cancers, including renal cell carcinoma, oral squamous cell carcinoma, prostate cancer, lung cancer, breast cancer, and multiple lymphocytic malignancies. In most of these cancers, β2m is correlated with more advanced disease and poorer prognosis. It has also been shown that in some cancer models, such as a renal cell carcinoma and an oral squamous cell carcinoma model, β2m can affect the proliferation and migration of these tumor cells. The levels and effects of β2m in pancreatic cancer, however, have not been reported thus far. Recent results from our laboratory have revealed high expression of β2m in nearly all members of a panel of pancreatic cancer cell lines. To examine the functional role that β2m plays in pancreatic cancer, we used siRNA specific for β2m to decrease its expression in the mentioned panel of pancreatic cancer cell lines and evaluated migration by transwell assay. Our results showed that the migration of the tested pancreatic cancer cell lines significantly decreases when β2m expression is reduced. Furthermore, we found that when β2m levels are downregulated, there are corresponding decreases in the levels of the HLA-A and -B heavy chains and in the expression of amyloid precursor-like protein 2 (APLP2). Previous research from our laboratory has shown that β2m affects APLP2/MHC association and that reducing expression of APLP2 slows pancreatic cancer cell migration. Additionally, our current research demonstrated that downregulation of β2m expression reduces the steady-state level and the half-life of APLP2. In conclusion, our results indicate that β2m promotes the migration of pancreatic cancer cells and suggest that this effect may be mediated through stabilization of the HLA class I heavy chain and, secondarily, APLP2. These studies thus provide evidence of β2m as a potential target for novel therapies directed against pancreatic cancer. Citation Format: Bailee Sliker, Cassie Liu, Brittany Poelaert, Benjamin Goetz, Joyce C. Solheim. Beta 2-microglobulin promotes human pancreatic cancer cell migration [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B028.