Abstract B032: The study of the role of Romo1 for angiogenesis/lymphangiogenesis in colorectal cancer

Reactive oxygen species modulator-1 (Romo1) is a novel protein that has been reported to be crucial for cancer cell proliferation and invasion. In a previous work, for the first time we reported that Romo1 correlated with poor survival of patients with colorectal cancer (CRC). In the current study, we investigated the role of Romo1 for angiogenesis/lymphangiogenesis in CRC. Romo1 overexpression in clinical tumor samples was associated with a high lymph node ratio between the metastatic and examined lymph nodes (p=0.025). IHC staining was used to demonstrate the Romo1 expression in clinical tissues. In the Matrigel invasion assay, cell invasiveness decreased in the Romo1 knockdown CRC cells compared with the controlled cells; this tendency was shown to be associated with epithelial-mesenchymal transition (EMT) induced by Romo1. We identified EMT markers at the protein levels in the Romo1-overexpressing cells. Epithelial marker E-cadherin was decreased while mesenchymal markers N-cadherin and Snail were increased in the Romo1-overexpressing cells compared with controlled cells. We also evaluated the mechanism by which Romo1 affects vascular endothelial growth factors (VEGF) transcription and promotes angiogenesis/lymphangiogenesis. The expression levels of VEGF were detected by real-time PCR and Western blot. We found that VEGF expression levels were upregulated in Romo1 overexpressed cells. Also in clinical tumor samples, Romo1 expression level determined by IHC staining was positively related with VEGF. Based on these results, we used Romo1 overexpressed cell’s conditional medium (CM) to culture the human umbilical vein endothelial cells (HUVEC), and detected the tube formation. We found that Romo1 overexpressing cell CM enhanced the tube formation compared with the control CM. In conclusion, lymphatic metastasis induced by Romo1 was a key reason for the poor survival associated with highly expressed Romo1 in CRC. We have shown that Romo1 not only promotes cancer invasion via EMT, but also has a direct role in lymphangiogenesis and/or angiogenesis. Citation Format: Hong Jun Kim, Dae-Hee Lee, Min Jee Jo, Sang Cheul Oh. The study of the role of Romo1 for angiogenesis/lymphangiogenesis in colorectal cancer [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 B032.