Correlation between the donor age and the proliferative lifespan of human peritoneal mesothelial cells in vitro: Is TGF-β1 a link?

Książek, Krzysztof; Winckiewicz, Marek; Staniszewski, Ryszard; Bręborowicz, Andrzej; Witowski, Janusz

doi:10.1016/j.exger.2007.04.012

Cited by 15 publications

(7 citation statements)

References 19 publications

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“…The similarity of the results as depicted in Figs. 2 and 3 confirms our earlier suggestions that HPMCs isolated from aged individuals may consist of a considerable fraction of replicatively senescent cells which have the ability to impose some phenotypical features of senescence on the whole culture [ 21 , 22 ]. Such a conclusion is in line with the observations of other authors who found that senescent fibroblasts modify the general characteristics of a culture when they constitute even only 10 % of the whole population [ 16 ].…”

Section: Resultssupporting

confidence: 83%

Senescent peritoneal mesothelium induces a pro-angiogenic phenotype in ovarian cancer cells in vitro and in a mouse xenograft model in vivo

Mikuła-Pietrasik

Sosińska

Naumowicz

et al. 2015

Clin Exp Metastasis

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It is believed that senescent cells contribute to the progression of primary and metastatic tumors, however, the exact mechanisms of this activity remain elusive. In this report we show that senescent human peritoneal mesothelial cells (HPMCs) alter the secretory profile of ovarian cancer cells (A2780, OVCAR-3, SKOV-3) by increasing the release of four angiogenic agents: CXCL1, CXCL8, HGF, and VEGF. Proliferation and migration of endothelial cells subjected to conditioned medium generated by: cancer cells modified by senescent HPMCs; cancer cells co-cultured with senescent HPMCs; and by early-passage HPMCs from aged donors, were markedly intensified. The same was the case for the vascularization, size and number of tumors that developed in the mouse peritoneum upon injection of ovarian cancer cells with senescent HPMCs. When the identified pro-angiogenic proteins were neutralized in conditioned medium from the cancer cells, both aspects of endothelial cell behavior intensified in vitro in response to senescent HPMCs were markedly reduced. The search for mediators of senescent HPMC activity using specific neutralizing antibodies and recombinant exogenous proteins showed that the intensified angiogenic potential of cancer cells was elicited by IL-6 and TGF-β1. At the transcriptional level, increased proliferation and migration of endothelial cells exposed to cancer cells modified by senescent HPMCs was regulated by HIF-1α, NF-κB/p50 and AP-1/c-Jun. Collectively, our findings indicate that senescent HPMCs may promote the progression of ovarian cancer cells by reprogramming their secretory phenotype towards increased production of pro-angiogenic agents and subsequent increase in the angiogenic capabilities of the vascular endothelium.

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Section: Resultssupporting

confidence: 83%

Senescent peritoneal mesothelium induces a pro-angiogenic phenotype in ovarian cancer cells in vitro and in a mouse xenograft model in vivo

Mikuła-Pietrasik

Sosińska

Naumowicz

et al. 2015

Clin Exp Metastasis

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“…The present study clearly demonstrated that donor age is the sole predictor of the replicative potential of human NPCs and that the replicative potential of human NPCs decreases with increasing age. This age-dependent decrease in replicative potential of human NPCs is in accordance with the results of other studies that used cells from different sources, including vascular smooth muscle cells [ 34 ], peritoneal mesothelial cells [ 35 ], adrenocortical cells [ 36 ], and peripheral blood mononuclear cells [ 37 ], although another previous study failed to find a correlation between the replicative potential of skin fibroblasts and donor age [ 33 ].…”

Section: Discussionsupporting

confidence: 89%

Relationship between Initial Telomere Length, Initial Telomerase Activity, Age, and Replicative Capacity of Nucleus Pulposus Chondrocytes in Human Intervertebral Discs: What Is a Predictor of Replicative Potential?

et al. 2015

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There is evidence that telomere length (TL), telomerase activity (TA), and age are related to the replicative potential of human nucleus pulposus chondrocytes (NPCs). However, it has not yet been established if any of these factors can serve as predictors of the replicative potential of NPCs. To establish predictors of the replicative potential of NPCs, we evaluated potential relationships between replicative capacity of NPCs, initial TL (telomere length at the first passage), initial TA (telomerase activity at the first passage), and age. Nucleus pulposus specimens were obtained from 14 patients of various ages undergoing discectomy. NPCs were serially cultivated until the end of their replicative lifespans. Relationships among cumulative population doubling level (PDL), initial TL, initial TA, and age were analyzed. Initial TA was negatively correlated with age (r = -0.674, P = 0.008). However, no correlation between initial TL and age was observed. Cumulative PDL was also negatively correlated with age (r = -0.585, P = 0.028). Although the cumulative PDL appeared to increase with initial TL or initial TA, this trend was not statistically significant. In conclusion, age is the sole predictor of the replicative potential of human NPCs, and replicative potential decreases with age. Initial TL and initial TA are not predictors of replicative potential, and can serve only as reference values.

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“…These include an age-dependent pattern of oxidative DNA damage intensification (Ksiazek et al 2008), an accumulation of senescent cells in the omentum in vivo (Ksiazek et al 2008b), and an inverse relationship between donor age and cell expandability in vitro (Ksiazek et al 2007b). On the other hand, despite senescence of these cells proceeds with increased expression of numerous markers of aging, including SA-β-Gal (Książek et al 2006), p16 INK4A (Ksiazek et al 2009b), p21 CIP1 (Ksiazek et al 2009b), 8-OH-dG (Książek et al 2006), lipofuscin (Ksiazek et al 2008c), and γ-H2A.X (Ksiazek et al 2007a), the attempts to identify a marker which would connect their senescence with organismal aging failed.…”

Section: Resultsmentioning

confidence: 99%

Specificity of cytochemical and fluorescence methods of senescence-associated β-galactosidase detection for ageing driven by replication and time

et al. 2014

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Senescence-associated β-galactosidase (SA-β-Gal) is a widely used marker of senescent cells in vitro and in vivo. In this report, young and senescent human peritoneal mesothelial cells (HPMCs) and fragments of the omentum, from which these cells were isolated, were subjected to simultaneous examination of SA-β-Gal using two methods, i.e. cytochemical and fluorescent methods. The results obtained were confronted with the cumulative number of population doublings (CPD) and the calendar age of the tissue donor. The study showed that senescence of HPMCs proceeds with either an increased percentage of SA-β-Gal-positive cells or increased enzyme activity. Cytochemical SA-β-Gal staining in early-passage cultures negatively correlated with CPD values but not with donor age in both cell cultures and omentum specimens. Conversely, SA-β-Gal activity measured with the fluorescence method rose in proportion to the calendar age of the donor either in early-passage cultures or in primary cell isolates from omental tissue. At the same time it was not related to the CPD values. These findings may suggest that with respect to at least peritoneal mesothelial cells, the cytochemical and fluorescent methods of SA-β-Gal detection, though complementary, are informative for different levels of aging, i.e. the cytochemical approach for senescence in vitro and the fluorescence-based technique for organismal aging in vivo.

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Correlation between the donor age and the proliferative lifespan of human peritoneal mesothelial cells in vitro: Is TGF-β1 a link?

Cited by 15 publications

References 19 publications

Senescent peritoneal mesothelium induces a pro-angiogenic phenotype in ovarian cancer cells in vitro and in a mouse xenograft model in vivo

Senescent peritoneal mesothelium induces a pro-angiogenic phenotype in ovarian cancer cells in vitro and in a mouse xenograft model in vivo

Relationship between Initial Telomere Length, Initial Telomerase Activity, Age, and Replicative Capacity of Nucleus Pulposus Chondrocytes in Human Intervertebral Discs: What Is a Predictor of Replicative Potential?

Specificity of cytochemical and fluorescence methods of senescence-associated β-galactosidase detection for ageing driven by replication and time

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