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and cooperate to drive metastasis by eliciting crosstalk between cancer and innate immunity. | LitMetric
Metastasis is a major cause of cancer mortality. We generated an autochthonous transgenic mouse model whereby conditional expression of and enables hepatocellular carcinoma (HCC) to metastasize in >90% of mice. and cooperate and their sustained expression is required to elicit a transcriptional program associated with the activation of innate immunity, through secretion of a cytokinome that elicits recruitment and polarization of tumor associated macrophages (TAMs). Systemic treatment with Ccl2 and Il13 induced -HCCs to metastasize; whereas, blockade of Ccl2 and Il13 abrogated /-HCC metastasis. Further, in 33 human cancers (n = 9502) and predict poor survival (p=4.3×10), CCL2/IL13 expression (p<10) and TAM infiltration (p<10). Finally, in the plasma of patients with HCC (n = 25) but not cirrhosis (n = 10), CCL2 and IL13 were increased and IL13 predicted invasive tumors. Therefore, and generally appear to cooperate in human cancer to elicit a cytokinome that enables metastasis through crosstalk between cancer and immune microenvironment.
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