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Sexual dimorphism of liver metastasis by murine pancreatic neuroendocrine tumors is affected by expression of complement C5
- Source :
- Oncotarget
- Publication Year :
- 2016
- Publisher :
- Impact Journals, LLC, 2016.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....aba636e4b862826214c48ac7720326ca