Abstract 1580: Cancer cells promote phenotypic alterations in adjacent hepatocytes to facilitate vessel co-option in colorectal cancer liver metastasis

Abstract

Abstract Vessel co-option is associated with resistance against anti-angiogenic therapy in colorectal cancer liver metastases (CRCLM). Vessel co-opted lesions are characterized by highly motile cancer cells that move toward and along the pre-existing vessels in the surrounding non-malignant tissue and hijack them to gain access to nutrient. In order to access the sinusoidal vessels, the cancer cells must displace the hepatocytes and occupy their space. However, the mechanisms underlying this displacement are unknown. Herein, we examined the involvement of apoptosis, motility, epithelial-mesenchymal transition (EMT) and autophagy pathways in hepatocyte’s displacement by cancer cells. We demonstrated that cancer cells induce the expression of the proteins that associated with upregulation of apoptosis, motility and EMT in adjacent hepatocytes in vitro and in vivo. Accordingly, we observed upregulation of cleaved caspase-3, cleaved poly (ADP-ribose) polymerase-1 (PARP-1) and Actin Related Protein 2/3 (ARP2/3) in adjacent hepatocytes to cancer cells, while we noticed lower expression levels of E-cadherin. Importantly, Runt-related transcription factor 1 (RUNX1) knockdown in the cancer cells has impaired their function towards adjacent hepatocytes in vitro and in vivo. Altogether, our data indicating that cancer cells may exploit various mechanisms to displace the hepatocytes and access to the sinusoidal vessels to establish vessel co-option. Citation Format: Miran Rada, Anthoula Lazaris, Peter Metrakos. Cancer cells promote phenotypic alterations in adjacent hepatocytes to facilitate vessel co-option in colorectal cancer liver metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1580.