Amigo2-upregulation in Tumour Cells Facilitates Their Attachment to Liver Endothelial Cells Resulting in Liver Metastases

Abstract

Since liver metastasis is the main cause of death in cancer patients, we attempted to identify the driver gene involved. QRsP-11 fibrosarcoma cells were injected into the spleens of syngeneic mice to isolate tumour sub-populations that colonize the liver. Cells from liver metastatic nodules were established and subsequently injected intrasplenically for selection. After 12 cycles, the cell subline LV12 was obtained. Intravenous injection of LV12 cells produced more liver metastases than QRsP-11 cells, whereas the incidence of lung metastases was similar to that of QRsP-11 cells. LV12 cells adhered to liver-derived but not to lung-derived endothelial cells. DNA chip analysis showed that amphoterin-induced gene and open reading frame 2 (Amigo2) was overexpressed in LV12 cells. siRNA-mediated knockdown of Amigo2 expression in LV12 cells attenuated liver endothelial cell adhesion. Ex vivo imaging showed that suppression of Amigo2 in luciferase-expressing LV12 cells reduced attachment/metastasis to liver to the same level as that observed with QRsP-11 cells. Forced expression of Amigo2 in QRsP-11 cells increased liver endothelial cell adhesion and liver metastasis. Additionally, Amigo2 expression in human cancers was higher in liver metastatic lesions than in primary lesions. Thus, Amigo2 regulated tumour cell adhesion to liver endothelial cells and formation of liver metastases.

Fraser extracellular matrix complex subunit 1 promotes liver metastasis of gastric cancer

“…Despite those data supporting our hypothesis, further investigation is required to conclude that FRAS1 specifically promotes liver metastasis. Assays of cell adhesion abilities to cultured liver endothelial cells, lung endothelial cells and peritoneal mesothelial cells can evaluate the metastatic directionality of cancer cells . Comparison of metastatic sites between orthotopic xenograft models by control GC cells and FRAS1 ‐KO cells might provide additional evidence .…”

“…Assays of cell adhesion abilities to cultured liver endothelial cells, lung endothelial cells and peritoneal mesothelial cells can evaluate the metastatic directionality of cancer cells. 52 Comparison of metastatic sites between orthotopic xenograft models by control GC cells and FRAS1-KO cells might provide additional evidence. 53 Moreover, modification of FRAS1 gene in the carcinogenic model mice may reveal the contribution of FRAS1 to formation of liver metastasis.…”

Harnessing BET Inhibitor Sensitivity Reveals AMIGO2 as a Melanoma Survival Gene

“…Our understanding of AMIGO2 function in cancer has been limited (Kanda et al, 2017; Park et al, 2015), likely due to the lack of evidence for genetic alterations. Here, we report that AMIGO2 is required for melanoma cell proliferation and survival and is induced by the acquisition of active cis DNA regulatory elements absent in NHMs.…”

Loss of the cystine/glutamate antiporter in melanoma abrogates tumor metastasis and markedly increases survival rates of mice

“…The tumor cell adhesion assay was performed according to a previously reported method 20. 2.13 | Cell migrationCell migration was evaluated by scratch assay based on the method of Liang with minor modifications 21.…”