Aging promotes neoplastic disease through effects on the tissue microenvironment

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Marongiu, Fabio, Paola Serra, Maria, Doratiotto, Silvia, Sini, Marcella, Fanti, Maura, Cadoni, Erika, Serra, Monica, Laconi, Ezio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5270675/
https://www.ncbi.nlm.nih.gov/pubmed/27929382
http://dx.doi.org/10.18632/aging.101128
_version_ 1782501209750372352
author Marongiu, Fabio
Paola Serra, Maria
Doratiotto, Silvia
Sini, Marcella
Fanti, Maura
Cadoni, Erika
Serra, Monica
Laconi, Ezio
author_facet Marongiu, Fabio
Paola Serra, Maria
Doratiotto, Silvia
Sini, Marcella
Fanti, Maura
Cadoni, Erika
Serra, Monica
Laconi, Ezio
author_sort Marongiu, Fabio
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5270675
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-52706752017-01-27 Aging promotes neoplastic disease through effects on the tissue microenvironment Marongiu, Fabio Paola Serra, Maria Doratiotto, Silvia Sini, Marcella Fanti, Maura Cadoni, Erika Serra, Monica Laconi, Ezio Aging (Albany NY) Research Paper 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. Impact Journals LLC 2016-12-06 /pmc/articles/PMC5270675/ /pubmed/27929382 http://dx.doi.org/10.18632/aging.101128 Text en Copyright: © 2016 Marongiu et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Marongiu, Fabio
Paola Serra, Maria
Doratiotto, Silvia
Sini, Marcella
Fanti, Maura
Cadoni, Erika
Serra, Monica
Laconi, Ezio
Aging promotes neoplastic disease through effects on the tissue microenvironment
title Aging promotes neoplastic disease through effects on the tissue microenvironment
title_full Aging promotes neoplastic disease through effects on the tissue microenvironment
title_fullStr Aging promotes neoplastic disease through effects on the tissue microenvironment
title_full_unstemmed Aging promotes neoplastic disease through effects on the tissue microenvironment
title_short Aging promotes neoplastic disease through effects on the tissue microenvironment
title_sort aging promotes neoplastic disease through effects on the tissue microenvironment
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5270675/
https://www.ncbi.nlm.nih.gov/pubmed/27929382
http://dx.doi.org/10.18632/aging.101128
work_keys_str_mv AT marongiufabio agingpromotesneoplasticdiseasethrougheffectsonthetissuemicroenvironment
AT paolaserramaria agingpromotesneoplasticdiseasethrougheffectsonthetissuemicroenvironment
AT doratiottosilvia agingpromotesneoplasticdiseasethrougheffectsonthetissuemicroenvironment
AT sinimarcella agingpromotesneoplasticdiseasethrougheffectsonthetissuemicroenvironment
AT fantimaura agingpromotesneoplasticdiseasethrougheffectsonthetissuemicroenvironment
AT cadonierika agingpromotesneoplasticdiseasethrougheffectsonthetissuemicroenvironment
AT serramonica agingpromotesneoplasticdiseasethrougheffectsonthetissuemicroenvironment
AT laconiezio agingpromotesneoplasticdiseasethrougheffectsonthetissuemicroenvironment