Sexual dimorphism of liver metastasis by murine pancreatic neuroendocrine tumors is affected by expression of complement C5
Autor: | Shinta Kobayashi, Laura H. Tang, Evan Vosburgh, Richard Clausen, Arnold J. Levine, Chang S. Chan, Tanupriya Contractor, Chris R. Harris, Edaise M da Silva |
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Rok vydání: | 2016 |
Předmět: |
Male
0301 basic medicine Pathology medicine.medical_specialty Mice Inbred Strains Complement C5a Neuroendocrine tumors Metastasis 03 medical and health sciences Sex Factors Animals Humans metastasis Medicine Receptor Mice Knockout Complement component 5 business.industry CD68 Macrophages Liver Neoplasms complement C5 medicine.disease Gene Expression Regulation Neoplastic Mice Inbred C57BL Pancreatic Neoplasms Sexual dimorphism Disease Models Animal Neuroendocrine Tumors 030104 developmental biology medicine.anatomical_structure Oncology pancreatic sexual dimorphism Female business Pancreas Research Paper |
Zdroj: | Oncotarget |
ISSN: | 1949-2553 |
DOI: | 10.18632/oncotarget.8874 |
Popis: | In a mouse model for neuroendocrine tumors of the pancreas (PanNETs), liver metastasis occurred at a higher frequency in males. Male mice also had higher serum and intratumoral levels of the innate immunity protein complement C5. In mice that lost the ability to express complement C5, there was a lower frequency of metastasis, and males no longer had a higher frequency of metastasis than females. Treatment with PMX53, a small molecule antagonist of C5aR1/CD88, the receptor for complement C5a, also reduced metastasis. Mice lacking a functional gene for complement C5 had smaller primary tumors, which were less invasive and lacked the CD68+ macrophages that have previously been associated with metastasis in this type of tumor. This is the first report of a gene that causes sexual dimorphism of metastasis in a mouse model. In the human disease, which also shows sexual dimorphism for metastasis, clinically advanced tumors expressed more complement C5 than less advanced tumors. |
Databáze: | OpenAIRE |
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