Panoply™ Human TREM2 Over-expressing Stable Cell Line

Triggering receptor expressed on myeloid cells 2 (TREM2) is involved in nonmalignant pathological processes. However, the function of TREM2 in malignant diseases, particularly hepatocellular carcinoma (HCC), remains unclear. Here, researchers report that TREM2 is a novel tumor suppressor in HCC. TREM2 expression is significantly reduced in HCC cells (especially metastatic HCC cells) and most human HCC tissues (especially extrahepatic metastatic tumors). Reduced TREM2 expression in tumors is associated with poor prognosis and aggressive pathological features in HCC patients (BCLC stage, tumor size, tumor capsule, vascular invasion, and tumor differentiation). Both in vitro and in vivo experiments showed that TREM2 knockdown significantly promotes cell proliferation, migration, and invasion, while TREM2 overexpression has the opposite effect. TREM2 inhibits HCC metastasis by suppressing epithelial-mesenchymal transition (EMT) and is accompanied by aberrant expression of epithelial and mesenchymal markers. Further research indicates that miR-31-5p regulates the downregulation of TREM2 expression in HCC. Furthermore, TREM2 inhibits the phosphorylation of Akt and GSK3β and activates β-catenin by directly interacting with β-catenin, thereby attenuating tumor carcinogenesis and metastasis. Therefore, TREM2 may be a potential prognostic biomarker for malignant tumors, and the restoration of TREM2 expression may be a promising therapeutic strategy for HCC.

To investigate the role of TREM2 in the progression of hepatocellular carcinoma (HCC), researchers constructed stable TREM2 knockdown and overexpression clones in MHCC97L cells (with a low lung metastasis rate of 40%) and MHCC97H cells (with a high lung metastasis rate of 100%), both derived from the same parental HCC cell line. Compared to the control group MHCC97L cells, the TREM2 knockdown cell line showed increased cell proliferation, while the TREM2 overexpression cell line exhibited suppressed cell viability (Figure 1a). Notably, the TREM2 knockdown cell line exhibited a more pronounced spindle-shaped and fibroblast-like morphology, with longer pseudopodia (Figure 1b). The suppression of TREM2 expression contributed to a substantial increase in cell motility, migration, and invasion ability of hepatoma cells, while TREM2 stable overexpression cells produced the opposite effect, as detected by scratch, transwell migration and invasion assays (Figure 1c, d).

Figure 1. TREM2 reduced oncogenic behaviors in HCC cells. (Tang W, et al., 2019)