uPAR Induces Expression of Transforming Growth Factor β and Interleukin-4 in Cancer Cells to Promote Tumor-Permissive Conditioning of Macrophages

Hu, Jingjing; Jo, Minji; Eastman, Boryana M.; Gilder, Andrew S.; Bui, Jack D.; Gonias, Steven L.

doi:10.1016/j.ajpath.2014.08.003

Cited by 34 publications

(32 citation statements)

References 49 publications

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“…Various inflammatory mediators in the blood direct mononuclear cells towards the wounded tissue for further differentiation into macrophages after the placement of biological materials. Activated macrophages clean the damaged and dead cells and bacteria through inflammatory processes (Arango Duque and Descoteaux, 2014;Hu et al, 2014). Additionally, numerous biologically active substances can guide tissue repair.…”

Section: Discussionmentioning

confidence: 99%

Macrophage proinflammatory response to the titanium alloy equipment in dental implantation

X¹,

Li²,

Yin³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Titanium alloy and stainless steel (SS) had been widely used as dental implant materials because of their affinity with epithelial tissue and connective tissue, and good physical, chemical, biological, mechanical properties and processability. We compared the effects of titanium alloy and SS on macrophage cytokine expression as well as their biocompatibility. Mouse macrophage RAW264.7 cells were cultured on titanium alloy and SS surfaces. Cells were counted by scanning electron microscopy. A nitride oxide kit was used to detect released nitric oxide by macrophages on the different materials. An enzyme linked immunosorbent assay was used to detect monocyte chemoattractant protein-1 levels. Scanning electron microscopy revealed fewer macrophages on the surface of titanium alloy (48.2 ± 6.4 x 10 3 cells/cm 2 ) than on SS (135 ± 7.3 x 10 3 cells/cm 2 ). The nitric oxide content stimulated by titanium alloy was 22.5 mM, which was lower than that stimulated by SS (26.8 mM), but the difference was not statistically significant (P = 0.07). The level of monocyte chemoattractant protein-1 released was significantly higher in the SS group (OD value = 0.128) than in the titanium alloy group (OD value = 0.081) (P = 9156 X. Chen et al.©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (3): 9155-9162 (2015) 0.024). The transforming growth factor-b1 mRNA expression levels in macrophages after stimulation by titanium alloy for 12 and 36 h were significantly higher than that after stimulation by SS (P = 0.31 and 0.25, respectively). Macrophages participate in the inflammatory response by regulating cytokines such as nitric oxide, monocyte chemoattractant protein-1, and transforming growth factor-b1. There were fewer macrophages and lower inflammation on the titanium alloy surface than on the SS surface. Titanium alloy materials exhibited better biological compatibility than did SS.

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Section: Discussionmentioning

confidence: 99%

Macrophage proinflammatory response to the titanium alloy equipment in dental implantation

X¹,

Li²,

Yin³

et al. 2015

Genet. Mol. Res.

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“…Interleukin (IL)-1, IL-4, IL-6, IL-8 and IL-10 (not shown), and Gas-6 are produced by OSCC cells and promote macrophage phenotype switching to an M2 polarization state. In turn, TAMs augment the recruitment of chemotactic receptors to tumour sites, induce tumour proliferation, and favour angiogenesis and invasiveness [31, 32, 36, 40–43, 47, 48, 65, 66] …”

Section: Introductionmentioning

confidence: 99%

Role of tumour-associated macrophages in oral squamous cells carcinoma progression: an update on current knowledge

et al. 2017

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BackgroundOral squamous cell carcinoma (OSCC) accounts over 90% of malignant neoplasms of the oral cavity. This pathological entity is associated to a high mortality rate that has remained unchanged over the past decades. Tumour-associated macrophages (TAMs) are believed to have potential involvement in OSCC progression. However, the molecular networks involved in communication between stroma and cancer cells have not yet been fully elucidated.Main bodyThe role of M2 polarized cells in oral carcinogenesis is supported by a correlation between TAMs accumulation into OSCC stroma and poor clinical outcome. Signalling pathways such as the NF-κB and cytokines released in the tumour microenvironment promote a bidirectional cross-talk between M2 and OSCC cells. These interactions consequently result in an increased proliferation of malignant cells and enhances aggressiveness, thus reducing patients’ survival time.ConclusionsHere, we present a comprehensive review of the role of interleukin (IL)-1, IL-4, IL-6, IL-8, IL-10 and the receptor tyrosine kinase Axl in macrophage polarization to an M2 phenotype and OSCC progression. Understanding the molecular basis of oral carcinogenesis and metastatic spread of OSCC would promote the development of targeted treatment contributing to a more favourable prognosis.

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“…Additionally, several proteases capable of degrading the surrounding tissue such as matrix metalloproteinases (MMPs) and components of the plasminogen activation system (uPAR, uPA, PAI-1 and plasmin) are secreted by different cell types or released from tissue matrix upon degradation and tissue remodeling [13,14]. uPAR has an ability to induce changes in the macrophages in the tumour microenvironment, which may be important for tumour progression [15]. Not only the cancer cells, but also the supporting stromal cells play a major role in tumour progression and further spread and the role of this extensive network of different cell types and signals must be revealed in order to enable development of future cancer therapies and response markers [16].…”

Section: Introductionmentioning

confidence: 99%

Inflammation and uPAR-Expression in Colorectal Liver Metastases in Relation to Growth Pattern and Neo-adjuvant Therapy

Eefsen

Engelholm

Alpízar‐Alpízar

et al. 2015

Cancer Microenvironment

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Proteolytic activity and inflammation in the tumour microenvironment affects cancer progression. In colorectal cancer (CRC) liver metastases it has been observed that three different immune profiles are present, as well as proteolytic activity, determined by the expression of urokinase-type plasminogen activator (uPAR).The main objectives of this study were to investigate uPAR expression and the density of macrophages (CD68) and T cells (CD3) as markers of inflammation in resected CRC liver metastases, where patients were neo-adjuvantly treated with chemotherapy with or without the angiogenesis inhibitor bevacizumab. Chemonaive patients served as a control group. The markers were correlated to growth patterns (GP) of liver metastases, i.e. desmoplastic, pushing and replacement GP. It was hypothesised that differences in proteolysis and inflammation could reflect tumour specific growth and therapy related changes in the tumour microenvironment. In chemonaive patients, a significantly higher level of uPAR was observed in desmoplastic liver metastases in comparison to pushing GP (p=0.01) or replacement GP (p=0.03). A significantly higher density of CD68 was observed in liver metastases with replacement GP in comparison to those with pushing GP (p=0.01). In liver metastases from chemo treated patients, CD68 density was significantly higher in desmoplastic GP in comparison to pushing GP (p=0.03). In chemo and bevacizumab treated patients only a significant lower CD3 expression was observed in liver metastases with a mixed GP than in those with desmoplastic (p= 0.01) or pushing GP (p=0.05). Expression of uPAR and the density of macrophages at the tumour margin of liver metastasis differ between GP in the untreated patients. A higher density of T cells was observed in the bevacizumab treated patients, when desmoplastic and pushing metastases were compared to liver metastases with a mix of the GP respectively, however no specific correlations between the immune markers of macrophages and T cells or GP of liver metastases could be demonstrated.

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uPAR Induces Expression of Transforming Growth Factor β and Interleukin-4 in Cancer Cells to Promote Tumor-Permissive Conditioning of Macrophages

Cited by 34 publications

References 49 publications

Macrophage proinflammatory response to the titanium alloy equipment in dental implantation

Macrophage proinflammatory response to the titanium alloy equipment in dental implantation

Role of tumour-associated macrophages in oral squamous cells carcinoma progression: an update on current knowledge

Inflammation and uPAR-Expression in Colorectal Liver Metastases in Relation to Growth Pattern and Neo-adjuvant Therapy

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