With Great Age Comes Great Metastatic Ability: Ovarian Cancer and the Appeal of the Aging Peritoneal Microenvironment

Age is one of the biggest risk factors for ovarian cancer. Older women have higher rates of diagnosis and death associated with the disease. In mouse models, it was shown that aged mice had greater tumor burden than their younger counterparts when intraperitoneally injected with ovarian tumor cells....

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Main Authors: Elizabeth I. Harper, Emma F. Sheedy, M. Sharon Stack
Format: Article
Language:English
Published: MDPI AG 2018-07-01
Series:Cancers
Subjects:
age
Online Access:http://www.mdpi.com/2072-6694/10/7/230
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spelling doaj-bf40a4ee2c704fbfbb15fea225c8a2812020-11-24T20:48:24ZengMDPI AGCancers2072-66942018-07-0110723010.3390/cancers10070230cancers10070230With Great Age Comes Great Metastatic Ability: Ovarian Cancer and the Appeal of the Aging Peritoneal MicroenvironmentElizabeth I. Harper0Emma F. Sheedy1M. Sharon Stack2Department of Chemistry and Biochemistry, University of Notre Dame, South Bend, IN 46617, USAHarper Cancer Research Institute, University of Notre Dame, South Bend, IN 46617, USADepartment of Chemistry and Biochemistry, University of Notre Dame, South Bend, IN 46617, USAAge is one of the biggest risk factors for ovarian cancer. Older women have higher rates of diagnosis and death associated with the disease. In mouse models, it was shown that aged mice had greater tumor burden than their younger counterparts when intraperitoneally injected with ovarian tumor cells. While very few papers have been published looking at the direct link between ovarian cancer metastasis and age, there is a wealth of information on how age affects metastatic microenvironments. Mesothelial cells, the peritoneal extracellular matrix (ECM), fibroblasts, adipocytes and immune cells all exhibit distinct changes with age. The aged peritoneum hosts a higher number of senescent cells than its younger counterpart, in both the mesothelium and the stroma. These senescent cells promote an inflammatory profile and overexpress Matrix Metalloproteinases (MMPs), which remodel the ECM. The aged ECM is also modified by dysregulated collagen and laminin synthesis, increases in age-related crosslinking and increasing ovarian cancer invasion into the matrix. These changes contribute to a vastly different microenvironment in young and aged models for circulating ovarian cancer cells, creating a more welcoming “soil”.http://www.mdpi.com/2072-6694/10/7/230ovarian canceragetumor microenvironmentextracellular matrixmesothelial cellsimmunefibroblastadipocytesperitoneum
collection DOAJ
language English
format Article
sources DOAJ
author Elizabeth I. Harper
Emma F. Sheedy
M. Sharon Stack
spellingShingle Elizabeth I. Harper
Emma F. Sheedy
M. Sharon Stack
With Great Age Comes Great Metastatic Ability: Ovarian Cancer and the Appeal of the Aging Peritoneal Microenvironment
Cancers
ovarian cancer
age
tumor microenvironment
extracellular matrix
mesothelial cells
immune
fibroblast
adipocytes
peritoneum
author_facet Elizabeth I. Harper
Emma F. Sheedy
M. Sharon Stack
author_sort Elizabeth I. Harper
title With Great Age Comes Great Metastatic Ability: Ovarian Cancer and the Appeal of the Aging Peritoneal Microenvironment
title_short With Great Age Comes Great Metastatic Ability: Ovarian Cancer and the Appeal of the Aging Peritoneal Microenvironment
title_full With Great Age Comes Great Metastatic Ability: Ovarian Cancer and the Appeal of the Aging Peritoneal Microenvironment
title_fullStr With Great Age Comes Great Metastatic Ability: Ovarian Cancer and the Appeal of the Aging Peritoneal Microenvironment
title_full_unstemmed With Great Age Comes Great Metastatic Ability: Ovarian Cancer and the Appeal of the Aging Peritoneal Microenvironment
title_sort with great age comes great metastatic ability: ovarian cancer and the appeal of the aging peritoneal microenvironment
publisher MDPI AG
series Cancers
issn 2072-6694
publishDate 2018-07-01
description Age is one of the biggest risk factors for ovarian cancer. Older women have higher rates of diagnosis and death associated with the disease. In mouse models, it was shown that aged mice had greater tumor burden than their younger counterparts when intraperitoneally injected with ovarian tumor cells. While very few papers have been published looking at the direct link between ovarian cancer metastasis and age, there is a wealth of information on how age affects metastatic microenvironments. Mesothelial cells, the peritoneal extracellular matrix (ECM), fibroblasts, adipocytes and immune cells all exhibit distinct changes with age. The aged peritoneum hosts a higher number of senescent cells than its younger counterpart, in both the mesothelium and the stroma. These senescent cells promote an inflammatory profile and overexpress Matrix Metalloproteinases (MMPs), which remodel the ECM. The aged ECM is also modified by dysregulated collagen and laminin synthesis, increases in age-related crosslinking and increasing ovarian cancer invasion into the matrix. These changes contribute to a vastly different microenvironment in young and aged models for circulating ovarian cancer cells, creating a more welcoming “soil”.
topic ovarian cancer
age
tumor microenvironment
extracellular matrix
mesothelial cells
immune
fibroblast
adipocytes
peritoneum
url http://www.mdpi.com/2072-6694/10/7/230
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