Aging promotes neoplastic disease through effects on the tissue microenvironment
Fabio Marongiu1, Maria Paola Serra1, Silvia Doratiotto1
1Department of Biomedical Sciences, Unit of Experimental Medicine, University of Cagliari, 09124, Cagliari, Italy.
Aging
|December 9, 2016
Summary
Aging enhances liver cancer development by altering the tissue microenvironment. Aged rat livers promoted preneoplastic cell growth, leading to tumor formation, unlike in young rats.
Area of Science:
- Oncology
- Aging Research
- Hepatology
Background:
- The relationship between aging and cancer (neoplasia) is complex and warrants further investigation.
- Aging may influence carcinogenesis through changes in the tissue microenvironment.
Purpose of the Study:
- To test the hypothesis that aging fuels carcinogenesis via alterations in the tissue microenvironment.
- To investigate the impact of the aged liver microenvironment on preneoplastic cell growth and tumor development.
Main Methods:
- Preneoplastic hepatocytes were isolated and orthotopically injected into young or old syngeneic rats.
- Donor-derived cells and tumor formation were tracked using the dipeptidyl-peptidase type IV (DPPIV) system.
- Senescence-associated β-galactosidase expression, IL6 mRNA, and protein levels were analyzed in aged and young rat livers.
Main Results:
- Hepatocytes injected into old rats formed significantly larger clusters (42±8 cells) compared to young rats (11±3 cells) at 3 months.
- While no lesions were found in young recipients after 8 months, 17/18 old recipients developed hepatic nodules or tumors.
- Aged rat livers showed increased senescence-associated β-galactosidase, IL6 mRNA, and IL6 protein compared to young controls.
Conclusions:
- The microenvironment of the aged liver promotes the growth and tumorigenesis of preneoplastic hepatocytes.
- Aging-associated changes, including senescence and elevated IL6, contribute to a pro-carcinogenic liver microenvironment.
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