Table 1.
The role of LSEC in primary and metastatic liver cancer
| Cancer | Target | Function | References |
|---|---|---|---|
| Melanoma and colorectal carcinoma | Notch signaling | Anti-ICAM1 antibody treatment significantly inhibited tumor cell adhesion to hepatic endothelial cells (HEC) in wild-type mice, which was associated with Notch signaling | [76] |
| Melanoma | CXCR4/CXCL12 axis | The metastasis of CXCR4-expressed murine melanoma B16 cells was associated with an increased expression of CXCL12 in LSEC microenvironments | [74] |
| Colon cancer | CXCR4/CXCL12 axis | The CXCR4/CXCL12 axis was involved in the formation of intrasplenic injection of colon cancer cells induced hepatic metastasis in nude Balb/c mice | [108] |
| Liver cancer | CXCR6/CXCL16 axis | Gut microbiota-mediated alteration of bile acid components can impact the CXCL16 expression in LSECs, resulted in the accumulation of CXCR6+ NKT cells to inhibit tumor growth | [67] |
| Colorectal cancer (CRC) | Intercellular Adhesion Molecule 1 (ICAM-1) | ICAM-1 blockade in the LSECs decreased the adhesion of cancer cells and their transmigration through LSEC monolayers in vitro and in vivo. In vitro, pre-stimulated tumor cells with soluble ICAM-1 increased 35% of liver colonization area than metastatic area induced by the untreated tumor cells | [75] |
| Colorectal cancer (CRC) | MicroRNA-20a | The microRNA-20a and its targeted proteins, such as E2F1 and Rho GTPase-activating protein 1 (ARHGAP1), were downregulated in LSECs from the liver with colorectal cancer metastasis compared to that in LSECs from a healthy liver | [88] |
| Colorectal carcinoma (CRC) | PD-L1 | Injection of circulating carcinoembryonic antigen (CEA) from colorectal carcinoma (CRC) cells resulted in CEA-specific CD8 T cells mediated LSECs in a PD-L1 dependent manner, but those antigen-specific CD8 T cells lost the tumoricidal effect on CEA-expressing cancer cells | [93] |
| Lewis lung carcinoma (LLC) | STAT3 | Activating STAT3 in murine endothelial MS-1 cells in vitro with tumor cell-conditioned media increased the expression of cell adhesion molecules, including E-selectin and P-selectin, which was also shown in pre-metastatic lungs of tumor-bearing mice in vivo. STAT3-knockdown in endothelial cells (ECs) reduced the metastasis of LLC cells in experimental and spontaneous metastasis murine models in vivo | [95] |