DIRECT INFLUENCES OF PRO-INFLAMMATORY CYTOKINES (IL-1β, TNF-α, IL-6) ON THE PROLIFERATION AND CELL-SURFACE ANTIGEN EXPRESSION OF CANCER CELLS

Kuninaka, Shinji; Yano, Tokujiro; Yokoyama, Hideki; Fukuyama, Yasuro; Terazaki, Yasuhiro; Uehara, Tadashi; Kanematsu, Takanori; Asoh, Hiroshi; Ichinose, Yukito

doi:10.1006/cyto.1998.0504

Cited by 50 publications

(42 citation statements)

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“…The inflammatory cytokines that have the most convincing tumor-promoting activity in a range of animal models are IL-6, IL-1b and tumor necrosis factor-a (TNFa); each of these cytokines can be considered as a therapeutic target (Kuninaka et al, 2000). In our study, their expression levels were also upregulated by LPS and by M-CSF þ MCP-1 and SAA.…”

Section: Fpr2 Regulates Tumorigenesismentioning

confidence: 64%

Pleiotropic regulation of macrophage polarization and tumorigenesis by formyl peptide receptor-2

et al. 2011

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Cancer cells recruit monocytes, macrophages and other inflammatory cells by producing abundant chemoattractants and growth factors, such as macrophage colony-stimulating factor (M-CSF/CSF-1) and monocyte chemoattractant protein-1 (MCP-1/CCL2), to promote tumor growth and dissemination. An understanding of the mechanisms that target cancer cells and regulate tumor microenvironment is essential in designing anticancer therapies. Here, we showed that serum amyloid-A (SAA) and cathelicidin (LL-37) stimulated M-CSF and MCP-1 expression with or without lipopolysaccharide (LPS) administration; conversely, lipoxin-A 4 (LXA 4 ) and annexin-A1 (ANXA1) inhibited LPS-induced M-CSF and MCP-1 production by human (HepG2) and mouse (H22) hepatocellular carcinoma cells (HCCs). The effects of LXA 4 , ANXA1, SAA and LL-37 were dependent on the activation of their mutual cell-surface receptor formyl peptide receptor-2 (FPR2) and subsequent ROS-MAPK-NF-kB signalings. Furthermore, our results indicated that LPS switched macrophages into an IL-10 low IL-12 high M1 profile, whereas M-CSF þ MCP-1 and FPR2 agonists skewed them into M2 (IL-10 high IL-12 low ). In that respect, through modulating the phosphorylation of signal transducer and activator of transcription-3 (STAT3), LXA 4 and ANXA1 induced monocyte differentiation into M2a þ M2c-like cells and showed antitumorigenetic activities, whereas SAA, LL-37 and M-CSF þ MCP-1 led to M2b-or M2d-like polarization, which exacerbated HCC invasion in vitro and in vivo, respectively. Our results suggest that FPR2 has an appreciable pleiotropic regulator role in tumor immunoediting.

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Section: Fpr2 Regulates Tumorigenesismentioning

confidence: 64%

Pleiotropic regulation of macrophage polarization and tumorigenesis by formyl peptide receptor-2

et al. 2011

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“…[29][30][31] We were therefore interested in determining whether this cytokine could be a mediator of the observed effects of anti-CD9 mAbs on colon carcinoma cell morphology and proliferation. For this purpose, we first assessed whether exogenous TNF-a was able to induce changes in the morphology and inhibition of proliferation similar to those caused by anti-CD9 mAbs.…”

Section: Tnf-a Is Involved In Morphological Changes and In Inhibitionmentioning

confidence: 99%

The tetraspanin CD9 inhibits the proliferation and tumorigenicity of human colon carcinoma cells

Ovalle

Gutiérrez-López

Olmo

et al. 2007

Intl Journal of Cancer

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The implication of the tetraspanin CD9 in cancer has received much recent attention and an inverse correlation between CD9 expression and the metastatic potential and cancer survival rate has been established for different tumor types. In contrast to the well-established role of CD9 in metastasis, very little is known about the involvement of this tetraspanin in the process of development of primary tumors. In the present study, we present evidence on the implication of CD9 in colon carcinoma tumorigenesis. We report here that ectopic expression of CD9 in colon carcinoma cells results in enhanced integrin-dependent adhesion and inhibition of cell growth. Consistently with these effects, treatment of these cells with anti-CD9-specific antibodies resulted in (i) increased b1 integrin-mediated cell adhesion through a mechanism involving clustering of integrin molecules rather than altered affinity; (ii) induction of morphological changes characterized by the acquisition of an elongated cell phenotype; (iii) inhibition of cell proliferation with no significant effect on cell survival; (iv) increased expression of membrane TNF-a, and finally (v) inhibition of the in vivo tumorigenic capacity in nude mice. In addition, through the use of selective blockers of TNF-a, we have demonstrated that this cytokine partly mediates the antiproliferative effects of CD9. These results clearly establish for the first time a role for CD9 in the tumorigenic process. ' 2007 Wiley-Liss, Inc.Key words: CD9; TNF-a; proliferation; tumorigenicity; tetraspanin The tetraspanin CD9 is a widely distributed surface molecule implicated in diverse functions, including cell signaling, growth, adhesion and motility, metastasis and sperm-egg fusion. Like other members of the tetraspanin protein family, CD9 participates in the organization of cell surface protein microdomains, termed ''the tetraspanin web,'' through association with other transmembrane proteins including members of the integrin family of adhesion receptors. [1][2][3] The implication of CD9 in cancer has received much attention. An inverse correlation between its expression in primary tumors and the metastatic potential and patient survival rate has been established for melanomas and colon, lung and breast carcinomas. 1,4-8 The involvement of this tetraspanin in tumor progression has been inferred from the effects of CD9 antibodies or CD9 overexpression on tumor cell motility and migration. In this regard, it has been shown that overexpression of this tetraspanin in melanoma and breast, lung, pancreas and colon carcinoma cells suppresses the motility and metastatic potential of these cells. 5,7,9,10 mAbs directed to the CD9 molecule have also been shown to inhibit the migration of different types of carcinoma tumor cells and the transendothelial migration of melanoma cells. 11-13 Therefore, the inverse correlation observed between CD9 expression and the metastatic potential could be explained, at least in part, by the effects mediated by CD9 on cell adhesion and migration through the ...

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“…The potent immunoregulatory cytokines interleukin-2 (IL-2) and interferon-g (IFN-g ) are crucial for the development of Th1 subset of T lymphocytes that are responsible for cellmediated immunity [3]. Alterations in pro-inflammatory cytokine production have been implicated in the pathophysiology of systemic inflammatory response syndrome (SIRS) [4], septic shock [5], acute respiratory distress syndrome (ARDS) [6,7], multiple organ dysfunction syndrome (MODS) [8], multiple trauma [9] and cancer [10]. Immunosuppression after major trauma results from T-cell dysfunction and is characterised by impaired synthesis of IL-2 and IFN-g [11].…”

mentioning

confidence: 99%

The immunomodulatory effects of prolonged intravenous infusion of propofol versus midazolam in critically ill surgical patients

Helmy

Al‐Attiyah

2001

Anaesthesia

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Both propofol and midazolam are known to inhibit immune function. The aim of this study was to investigate cytokine production in critically ill surgical patients as early markers of immune response to prolonged infusion of propofol and midazolam. The study enrolled 40 elective patients who were to receive long‐term sedation for more than 2 days. Patients were randomly allocated to one of two equally sized groups. Central venous blood samples for measurement of interleukin‐1β (IL‐1β), interleukin‐2 (IL‐2), interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), tumour necrosis factor‐α (TNF‐α) and interferon‐γ (IFN‐γ) were drawn prior to the start and after 48 h of infusion. After 48 h, propofol caused significant increases in IL‐1β (24%), IL‐6 (23%) and TNF‐α (4.8 times) levels, while midazolam caused significant decreases in IL‐1β (21%), IL‐6 (21%) and TNF‐α (19%). Both agents caused significant decreases in IL‐8 levels (propofol: 30%, midazolam: 48%, p < 0.05). Propofol caused significant decreases in IL‐2 levels (68%, p < 0.001) but increases in IFN‐γ (30%, p < 0.05), whereas there was no significant change with midazolam compared with the pre‐infusion level. In conclusion, during 48 h of continuous infusion, propofol stimulated, while midazolam suppressed, the production of the pro‐inflammatory cytokines IL‐1β, IL‐6 and TNF‐α, and both caused suppression of IL‐8 production. Propofol inhibited IL‐2 production and stimulated IFN‐γ production, whereas midazolam failed to do so. Therefore, sedative agents may have clinical implications in high‐risk and immunocompromised patients.

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DIRECT INFLUENCES OF PRO-INFLAMMATORY CYTOKINES (IL-1β, TNF-α, IL-6) ON THE PROLIFERATION AND CELL-SURFACE ANTIGEN EXPRESSION OF CANCER CELLS

Cited by 50 publications

References 13 publications

Pleiotropic regulation of macrophage polarization and tumorigenesis by formyl peptide receptor-2

Pleiotropic regulation of macrophage polarization and tumorigenesis by formyl peptide receptor-2

The tetraspanin CD9 inhibits the proliferation and tumorigenicity of human colon carcinoma cells

The immunomodulatory effects of prolonged intravenous infusion of propofol versus midazolam in critically ill surgical patients

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