title: Aging promotes neoplastic disease through effects on the tissue microenvironment.
abstract: A better understanding of the complex relationship between aging and cancer will provide important tools for the prevention and treatment of neoplasia. In these studies, the hypothesis was tested that aging may fuel carcinogenesis via alterations imposed in the tissue microenvironment. Preneoplastic hepatocytes isolated from liver nodules were orthotopically injected into either young or old syngeneic rats and their fate was followed over time using the dipeptidyl-peptidase type IV (DPPIV) system to track donor-derived-cells. At 3 months post-Tx, the mean size of donor-derived clusters was 11±3 cells in young vs. 42±8 in old recipients. At 8 months post-Tx, no visible lesion were detected in any of 21 young recipients, while 17/18 animals transplanted at old age displayed hepatic nodules, including 7 large tumors. All tumors expressed the DPPIV marker enzyme, indicating that they originated from transplanted cells. Expression of senescence-associated β-galactosidase was common in liver of 18-month old animals, while it was a rare finding in young controls. Finally, both mRNA and IL6 protein were found to be increased in the liver of aged rats compared to young controls. These results are interpreted to indicate that the microenvironment of the aged liver promotes the growth of pre-neoplastic hepatocytes.
authors.affiliation: Department of Biomedical Sciences, Unit of Experimental Medicine, University of Cagliari, 09124, Cagliari, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Marongiu
authors.affiliation: Department of Biomedical Sciences, Unit of Experimental Medicine, University of Cagliari, 09124, Cagliari, Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Serra
authors.affiliation: Department of Biomedical Sciences, Unit of Experimental Medicine, University of Cagliari, 09124, Cagliari, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Doratiotto
authors.affiliation: Department of Biomedical Sciences, Unit of Experimental Medicine, University of Cagliari, 09124, Cagliari, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Sini
authors.affiliation: Department of Biomedical Sciences, Unit of Experimental Medicine, University of Cagliari, 09124, Cagliari, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Fanti
authors.affiliation: Department of Biomedical Sciences, Unit of Experimental Medicine, University of Cagliari, 09124, Cagliari, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Cadoni
authors.affiliation: Department of Biomedical Sciences, Unit of Experimental Medicine, University of Cagliari, 09124, Cagliari, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Serra
authors.affiliation: Department of Biomedical Sciences, Unit of Experimental Medicine, University of Cagliari, 09124, Cagliari, Italy.
authors.forename: Ezio
authors.initials: E
authors.lastname: Laconi
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D022781:Hepatocytes / Q000473:pathology; D008099:Liver; D008114:Liver Neoplasms, Experimental / Q000473:pathology*; D011230:Precancerous Conditions; D051381:Rats; D011916:Rats, Inbred F344
keywords: aging; liver carcinogenesis; microenvironment; pre-neoplastic hepatocytes; selection