Abstract 5160: Identifying TK1 localization in immortalized placental cell lines and in conditioned placental tissue

Abstract

Abstract Many parallels in growth pattern can be observed between placental and cancer development. In fact, placental trophoblast and cancer cells share similarities in migration and invasion patterns, immune escape strategies, and angiogenesis induction. A common feature of pregnancy complication is aberrant trophoblast behavior. Understanding trophoblast cell behavior can help us identify common patterns in cancer gene and protein regulation. Thymidine kinase 1 (TK1) has been extensively studied as a serum and tissue cancer biomarker. Recently, TK1 has been shown to be upregulated in some cancer tissues and localized on the surface of certain cancer cell lines, and has been suggested as a possible immunotherapeutic target in some cancers. Our goal for this study was to investigate TK1 correlation to placental invasive potential, and therefore establish a function for TK1 localization in these tissues. To do this, we wanted to investigate TK1 placental tissue expression/ localization during normal and obstetric complications and its expression in current placental cell lines. We obtained human placental tissue from various pregnancy conditions including preeclampsia (PE), diabetes (GDM; treated with diet (D) or Insulin (I)) and intrauterine growth restriction (IUGR). For our cell study, immortalized placental cell lines, SW71, JEG-3 and BeWo were used. Immunofluorescence was used for TK1 cell expression in human placental sections. Flow cytometry was performed for TK1 presence in cultured cells. We observed high staining for nuclear and cytosolic expression of TK1 in the control placenta tissues. Compared to controls, there was a marked reduction in TK1 staining in the IUGR and GDM-I placentas which lack nuclear expression of TK1. A decreased for both nuclear and cytosolic TK1 staining, was present in the PE and GDM-D placenta. Flow cytometry showed that SW71 cells had high expression of TK1 on their surface (56%), JEG-3 had low expression of TK1 on their surface (12%), and BeWo cells did not express TK1 on their surface. These findings are interesting because they suggest TK1 surface expression directly correlates with the invasive potential. TK1 protein expression was also measured using standard western blotting techniques to support the data obtained by immunohistochemistry. Furthermore, we established the invasion potential of these placental cell lines using the xCELLigence RTCA DP system between the TK1 positive and negative placenta cell lines. Further confirmation is required; however, these results could assist in understanding the placental/trophoblast invasive mechanism and its correlation in cancer development. Citation Format: Eliza E. Lawrence, Evita G. Weagel, Juan F. Mejia, Juan Arroyo, Shalee Killpack, Kim L. O'Neill, Richard Robison. Identifying TK1 localization in immortalized placental cell lines and in conditioned placental tissue [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5160.