Host Cxcr2-Dependent Regulation of Pancreatic Cancer Growth, Angiogenesis, and Metastasis
| Autor: | Michelle L. Varney, Sugandha Saxena, Jessica A. Kozel, Dipakkumar R. Prajapati, Rakesh K. Singh, Abhilasha Purohit, Audrey Lazenby |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine Chemokine Myeloid Neutrophils Angiogenesis Receptors Interleukin-8B Pathology and Forensic Medicine Metastasis Mice 03 medical and health sciences 0302 clinical medicine Immune system Cell Line Tumor Pancreatic cancer Tumor Microenvironment medicine Animals CXC chemokine receptors Neoplasm Metastasis Cell Proliferation Innate immune system Neovascularization Pathologic biology Chemistry Endothelial Cells Regular Article hemic and immune systems respiratory system medicine.disease biological factors respiratory tract diseases Pancreatic Neoplasms 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research biology.protein |
| Zdroj: | Am J Pathol |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2021.01.002 |
| Popis: | Pancreatic ductal adenocarcinoma (PDAC) manifests aggressive tumor growth and early metastasis. Crucial steps in tumor growth and metastasis are survival, angiogenesis, invasion, and immunosuppression. Our prior research showed that chemokine CXC- receptor-2 (CXCR2) is expressed on endothelial cells, innate immune cells, and fibroblasts, and regulates angiogenesis and immune responses. Here, we examined whether tumor angiogenesis, growth, and metastasis of CXCR2 ligands expressing PDAC cells are regulated in vivo by a host CXCR2-dependent mechanism. C57BL6 Cxcr2(−/−) mice were generated following crosses between Cxcr2(−/+) female and Cxcr2(−/−) male. Cxcr2 ligands expressing Kirsten rat sarcoma (KRAS-PDAC) cells were orthotopically implanted in the pancreas of wild-type or Cxcr2(−/−) C57BL6 mice. No significant difference in PDAC tumor growth was observed. Host Cxcr2 loss led to an inhibition in microvessel density in PDAC tumors. Interestingly, an enhanced spontaneous and experimental liver metastasis was observed in Cxcr2(−/−) mice compared with wild-type 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. |
| Databáze: | OpenAIRE |
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