Fig. 4.

Axl receptor tyrosine kinase as a potential therapeutic target revealed by inhibitor screening assay and in vivo mouse study. A, the heat map shows the differential sensitivity of metastatic pancreatic cancer cells derived from peritoneum, lung, and liver to small molecule inhibitors. B, mice xenografted with metastatic pancreatic cancer cells derived from lung and liver were more sensitive to R428, a small molecule inhibitor to Axl receptor tyrosine kinase in vivo mouse model, than mice xenografted with cells derived from peritoneum. C, five representative immunohistochemistry images of Axl staining on matched primary and metastatic pancreatic cancers from five different patients are depicted (A31, A29, A55, A89, and A92). A31 is an example of low expression in the primary and matched metastasis. The arrow in A31 primary indicates strong positive labeling of endothelium within a small capillary, as compared with negative labeling of the neoplastic cells. The negative labeled cancer cells are circled with a dashed line in A31 metastasis. A29 is an example of strong positive labeling in the primary carcinoma and weak labeling in the metastasis. By contrast, A55 is an example of weak labeling in the primary and strong labeling in the metastasis. A89 and A92 are examples of strong positive labeling in both the primary and the matched metastasis. The arrow in the A89 metastasis indicates a negative labeled normal bile duct.