The Aged Microenvironment Influences the Tumorigenic Potential of Malignant Prostate Epithelial Cells

Bianchi‐Frias, Daniella; Damodarasamy, Mamatha; Hernández, Susana; Costa, Rui M. Gil da; Vakar-López, Funda; Coleman, Ilsa M.; Reed, May J.; Nelson, Peter S.

doi:10.1158/1541-7786.mcr-18-0522

Cited by 36 publications

(34 citation statements)

References 38 publications

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“…Furthermore, we have shown that peritoneal macrophages that originate from either aged (26 months) C57BL/6J female mice or Balb/c female mice (18 months) stimulated with tumor-derived factors increased production of TGF-β1 and IL-4, relative to macrophages from young mice [32,53]. In a prostate cancer model, transcriptomic analysis of the tumor microenvironment revealed an increase in the expression of genes associated with protumorigenic macrophages, such as Arg1 Cd163, Mrc1, Retnla, Lyve1, in aged (20-24 months) compared to young male C57BL/6J mice [117]. Similarly, in human prostate cancer there was an increase in expression of CD163, a monocyte and macrophage-specific scavenger receptor, in elderly patients which corresponded with poorer survival [117].…”

Section: Macrophages In Cancer and Ageingmentioning

confidence: 99%

Macrophage function in the elderly and impact on injury repair and cancer

et al. 2021

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Older age is associated with deteriorating health, including escalating risk of diseases such as cancer, and a diminished ability to repair following injury. This rise in age-related diseases/co-morbidities is associated with changes to immune function, including in myeloid cells, and is related to immunosenescence. Immunosenescence reflects age-related changes associated with immune dysfunction and is accompanied by low-grade chronic inflammation or inflammageing. This is characterised by increased levels of circulating pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1β and IL-6. However, in healthy ageing, there is a concomitant age-related escalation in anti-inflammatory cytokines such as transforming growth factor-β1 (TGF-β1) and IL-10, which may overcompensate to regulate the pro-inflammatory state. Key inflammatory cells, macrophages, play a role in cancer development and injury repair in young hosts, and we propose that their role in ageing in these scenarios may be more profound. Imbalanced pro- and anti-inflammatory factors during ageing may also have a significant influence on macrophage function and further impact the severity of age-related diseases in which macrophages are known to play a key role. In this brief review we summarise studies describing changes to inflammatory function of macrophages (from various tissues and across sexes) during healthy ageing. We also describe age-related diseases/co-morbidities where macrophages are known to play a key role, focussed on injury repair processes and cancer, plus comment briefly on strategies to correct for these age-related changes.

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Section: Macrophages In Cancer and Ageingmentioning

confidence: 99%

Macrophage function in the elderly and impact on injury repair and cancer

et al. 2021

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“…Meroterpenoids Ehrlich's tumor exhibits strong inflammatory phenomena, including edema and inflammatory infiltrates, which are believed to play an essential role in tumor growth in various types of cancer [42,43,44,45,46]. But the anti-inflammatory effects were reported by meroterpenoids [47] and were observed in this research showing that the extract reduces inflammation, reducing the tumor by an indirect route.…”

Section: P Purpurogenum Extract Showed Activity Against Ehrlich's Somentioning

confidence: 60%

“…Tregs is observed in tumor tissues, and their depletion augments antitumor immune responses in animal models [44].…”

Section: P Purpurogenum Extract Showed Activity Against Ehrlich's Somentioning

confidence: 99%

Penicillium purpurogenumexerts antitumor effects and ameliorates inflammations in Erlich mice model

Teles

Pontes

Guimarães

et al. 2020

Preprint

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ABSTRACTBackgroundThe bioactive metabolites production contributes to the resistance of fungi towards adverse environmental conditions. Some metabolites often have interesting health-promoting activities. This study addressed the anti-tumoural properties of Penicillium purpurogenum isolated from a polluted lagoon in Northeastern Brazil.MethodsThe extract obtained from the polished environment strain P. purpurogenum was fermented, filtered, concentrated and lyophilized, giving rise to the Ethyl Acetate Extracellular Extract (EAE). The metabolites of the extracellular extract of P. purpurogenum were studied using direct infusion mass spectrometry. The solid Ehrlic tumor model was used to evaluate the extract antitumor activity. Female Swiss mice were divided in groups (n=10/group) as follow: Negative control (CTL-) treated with phosphate buffered solution; Positive Control (CTL+) treated with cyclophosphamide (25mg/mL); Extracts treatment at doses 4, 20 and 100mg/Kg; Animals without tumor or treatment (Sham); and animals without tumor treated with intermediate dose (EAE20). All treatments were performed intraperitoneally, daily during 15 days. After, the animals were eutanized and the tumor, lymphoid organs and serum were used for immunological, histological and biochemical parameters evaluation.ResultsThe extract was rich in meroterpenoids. All doses of the extract significantly reduced tumor size compared to CLT- and were associated with 100% survival. Histologically, the 20 and 100mg/kg doses reduced tumour-associated inflammation and tumour necrosis. The extract also reduced cellular infiltration of lymphoid organs and circulating TNF-α levels when compared with CLT-. The extract did not induce weight loss and renal or hepatic toxic changes.ConclusionsThese results indicate that P. purpurogenum from a polluted marine environment produce hybrid natural products of the terpenoid pathway that exhibits immunomodulatory and antitumor properties in vivo. Thus, fungal fermentation is a biotechnological approach for the production of antitumour agents.

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“…expression within the tumor microenvironment is associated with increased tumor growth and poor prognostic outcomes for several cancers (Bianchi-Frias et al, 2018;Byun et al, 2017;Roh et al, 2017;Xu, Jiang, et al, 2015). VSIG4 may play a direct role in cancer progression, as Vsig4 deficiency was shown to suppress the growth of Lewis lung carcinoma (LLC1) isografts (Liao et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…VSIG4, an immune checkpoint protein, is thought to enable the cancer progression through suppression of T-lymphocyte activation(Bianchi-Frias et al, 2019;Liao et al, 2014). NIH Swiss mice exhibit a relatively high incidence of spontaneous lung cancer with age.…”

mentioning

confidence: 99%