Abstract 34: The receptor for hyaluronan acid mediator motility (RHAMM, CD168) expression in EMT-like cancer cells is a predictor of tumor progression in colorectal cancer

Abstract

Abstract Background/Aim: The receptor for hyaluronan acid mediator motility (RHAMM) is a marker of tumor progression and decreased overall survival in patients with different solid tumor types. The aim of the present study was to investigate the functional and clinical role of RHAMM in colorectal cancer (CRC) using in vitro and in vivo models and to validate the results on a cohort (n=200) of CRC patients with full clinico-pathological features. Material and Methods: Two established CRC cell lines HT29 and HT116 (mismatch-repair proficient and deficient) expressing RHAMM by flow-cytometry were selected for proliferation, invasion and migration assays. For the in vivo analysis tumor cells were injected in immune-deficient NOD/SCID mice. RHAMM expression was additionally analyzed by immunohistochemistry on 200 CRC whole tissue sections, with particular focus on the single, detached and aggressive EMT-like cells at the invasion front and correlated to clinicopathological data and survival. Results: In vitro, RHAMM silenced HT29 and HCT116 cell lines showed a significant decrease in invasiveness and migration compared to untreated cells. In vivo, a lower tumorigenicity of HT29 and HT116 cells silenced for RHAMM compared to untreated cells was reflected by smaller tumor volumes in the injected immune-deficient NOD/SCID mice. In the immunohistochemical analysis RHAMM expression in EMT-like cancer cells was associated with lymphatic invasion (p=0.0013), higher tumor grade (p=0.021) and worse survival (p=0.034). Conclusion: In vitro and in vivo findings as well as results on clinical patient data support the notion that over-expression of RHAMM is involved in tumor progression in CRC and highlight a promising basis for a therapeutic approach. Citation Format: Valentina Mele, Viktor H. Koelzer, Bettina Huber, Manuele G. Muraro, Dennis Pfaff, Giandomenica Iezzi, Luigi M. Terracciano, Eva Karamitopoulou, Inti Zlobec, Alessandro Lugli. The receptor for hyaluronan acid mediator motility (RHAMM, CD168) expression in EMT-like cancer cells is a predictor of tumor progression in colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 34. doi:10.1158/1538-7445.AM2014-34