Pancreatic ductal adenocarcinoma (PDAC) manifests aggressive tumor growth and early metastasis. Crucial steps in tumor growth and metastasis are survival, angiogenesis, invasion, and immunosuppression. Previously we have shown that CXCR2 is expressed on endothelial cells, innate immune cells, and fibroblasts and regulates angiogenesis and immune responses. In this report, we examined whether tumor angiogenesis, growth, and metastasis of CXCR2-ligands expressing PDAC cells are regulated in vivo by a host CXCR2-dependent mechanism. We generated C57BL6 Cxcr2 mice following crosses between Cxcr2 female and Cxcr2 male. We orthotopically implanted Cxcr2-ligands expressing KRAS-PDAC cells in the pancreas of wild-type (WT) or Cxcr2 C57BL6 mice. No significant difference in PDAC tumor growth was observed. Host Cxcr2 loss led to inhibition in microvessel density in PDAC tumors. Interestingly, an enhanced spontaneous and experimental liver metastasis was observed in Cxcr2 mice as compared to WT mice. Increased metastasis in Cxcr2 mice was associated with an increase in extramedullary hematopoiesis and expansion of neutrophils and immature myeloid precursor cells in the spleen of tumor-bearing mice. These data suggest a dynamic role of host CXCR2 axis in regulating tumor immune suppression, tumor growth, and metastasis.
Copyright © 2021. Published by Elsevier Inc.

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