Expression of Interleukin‐22 in Murine Carcinoma Cells did not Influence Tumour Growth <i>In Vivo</i> but did Improve Survival of the Inoculated Hosts

Nagakawa, Hiroyasu; Shimozato, Osamu; Yu, Ling; Takiguchi, Yuichi; Kuriyama, Takayuki; Tagawa, Masatoshi

doi:10.1111/j.0300-9475.2004.01504.x

Cited by 21 publications

(10 citation statements)

References 17 publications

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“…Although the growth of IL-22-transfected colon 26 cells was not different from that of control cells in vitro, survival of inoculated mice was significantly prolonged compared with control mice, suggesting that IL-22 might play a protective role in the mice with colon carcinoma (15). In contrast, Weber et al (16) reported that IL-22 reduced EMT6 murine breast tumor growth by inhibiting ERK1/2 and AKT phosphorylation.…”

Section: Discussionmentioning

confidence: 93%

Antiapoptotic Activity of Autocrine Interleukin-22 and Therapeutic Effects of Interleukin-22-Small Interfering RNA on Human Lung Cancer Xenografts

Zhang

Chen

Wei

et al. 2008

Clinical Cancer Research

108

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Purpose: Non^small cell lung carcinoma (NSCLC) is one of most common malignant diseases and usually is resistant against apoptosis-inducing chemotherapy. This study is to explore the antiapoptotic mechanisms of interleukin (IL)-22 in human lung cancer. Experimental Design: Nineteen cases with stage I to III NSCLC were collected to determine the expression of IL-22. Stable transfection of human IL-22 cDNA into A549 and PG cells and transfection of IL-22-RNA interference (RNAi) into these cancer cell lines were done to reveal the molecular mechanisms of IL-22. Results: It was found that IL-22 was highly expressed in primary tumor tissue, malignant pleural effusion, and serum of patients with NSCLC. IL-22R1 mRNA was also detected in lung cancer tissues as well as lung cancer cell lines. Overexpression of IL-22 protected lung cancer cell lines from serum starvation-induced and chemotherapeutic drug-induced apoptosis via activation of STAT3 and its downstream antiapoptotic proteins such as Bcl-2 and Bcl-xL and inactivation of extracellular signal-regulated kinase 1/2. Exposure to blocking antibodies against IL-22R1 or transfection with the IL-22-RNAi plasmid in vitro resulted in apoptosis of these lung cancer cells via STAT3 and extracellular signal-regulated kinase 1/2 pathways. Furthermore, an in vivo xenograft study showed that administration of IL-22-RNAi plasmids significantly inhibited the human tumor cell growth in BALB/c nude mice. Conclusions: Our study indicates that autocrine production of IL-22 contributes to human lung cancer cell survival and resistance to chemotherapy through the up-regulation of antiapoptotic proteins.

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Section: Discussionmentioning

confidence: 93%

Antiapoptotic Activity of Autocrine Interleukin-22 and Therapeutic Effects of Interleukin-22-Small Interfering RNA on Human Lung Cancer Xenografts

Zhang

Chen

Wei

et al. 2008

Clinical Cancer Research

108

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“…IL-22 promoted the growth of cancer cells in some models but not in others. In a colon carcinoma 26 (CC26) syngeneic tumour model, IL-22 did not affect either tumour growth or metastasis 163 . Tumour-promoting effects have been described for both IL-20 and IL-26.…”

Section: Il-20 Subfamily Cytokines In Cancermentioning

confidence: 93%

“…For example, IL-20RA and IL-20RB are expressed on non-small-cell lung cancer, breast cancer, bladder cancer and oral cancer cells [158][159][160][161][162] . IL-22RA1 is detected in colorectal, skin, pancreatic, liver and lung cancers [163][164][165] .…”

Section: Il-20 Subfamily Cytokines In Cancermentioning

confidence: 99%

The IL-20 subfamily of cytokines — from host defence to tissue homeostasis

Rutz¹,

Wang²,

Ouyang³

2014

Nat Rev Immunol

305

326

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The interleukin-20 (IL-20) subfamily of cytokines comprises IL-19, IL-20, IL-22, IL-24 and IL-26. These cytokines are all members of the larger IL-10 family, but have been grouped together to form the IL-20 subfamily based on their usage of common receptor subunits and similarities in their target-cell profiles and biological functions. Members of the IL-20 subfamily facilitate the communication between leukocytes and epithelial cells, thereby enhancing innate defence mechanisms and tissue repair processes at epithelial surfaces. In this Review, we describe the cellular sources and targets of the IL-20 subfamily cytokines, and we detail how their expression is regulated. Much of our understanding of the unique biology of this group of cytokines is still based on IL-22, which is the most studied member of the IL-20 subfamily. Nevertheless, we attempt a broader discussion of the emerging functions of IL-20 subfamily cytokines in host defence, inflammatory diseases, cancer and metabolism.

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“…Although the growth of Colon 26/IL-22 tumors in syngeneic mice did not differ from that of parent tumors, survival of mice inoculated with Colon 26/IL-22 tumors was significantly prolonged compared with the survival of mice inoculated with parent tumors [26]. IL-22 inhibited the growth of human mammary adenocarcinoma EMT6 cells both in vivo and in vitro [27].…”

Section: Introductionmentioning

confidence: 90%

Interleukin-22 Suppresses the Growth of A498 Renal Cell Carcinoma Cells via Regulation of STAT1 Pathway

et al. 2011

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BackgroundRenal cell carcinoma (RCC) is one of the most common kidney cancers and is highly resistant to chemotherapy. Accumulating evidence suggests that interleukin-22 (IL-22) may mediate host defense against varietal pathogens as a proinflammatory and anti-inflammatory cytokine. The purpose of this study is to assess the inhibitory effects of IL-22 on human RCC cell line A498 and to investigate the possible mechanisms underlying the anti-tumor effects of this cytokine.MethodologyA498 cells, a RCC cell line, were used to assess the inhibitory growth effects of IL-22 using the MTT assay and flow cytometric analysis in vitro. BALB/C nude mice bearing A498 cell xenografts were used to examine the antitumor efficacy of IL-22 in vivo. Western blotting assay was performed to detect the regulation of the intracellular signaling pathway of IL-22.Principal FindingsWe found that IL-22 suppressed the growth of A498 cells in a dose-dependent manner and inhibited the growth of A498 xenografts. We also observed that IL-22 produced a dose-dependent inhibitory effect on A498 cells that involved the induction of G2/M cell cycle arrest without cell apoptosis. Moreover, we showed that the phosphorylation of STAT1 was increased and the phosphorylation of ERK1/2 was attenuated in A498 cells exposed to IL-22. The growth inhibition of A498 cells was partially revised after IL-22 treatment as the expression of STAT1 was knocked down. And inflammatory cytokines, interferon-α and tumor necrosis factor-α (TNF-α) were barely involved in the suppression of A498 cell xenografts treated with IL-22.ConclusionsIL-22 dose-dependently suppresses RCC cell line A498 cells in vitro and induces growth inhibition of A498 cell-bearing mouse xenografts. These results suggest that the anti-RCC effects of IL-22 are at least partially mediated through regulation of STAT1 signaling pathways and G2/M cell cycle arrest, rather than by inducing apoptosis and inflammatory cytokines.

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Expression of Interleukin‐22 in Murine Carcinoma Cells did not Influence Tumour Growth In Vivo but did Improve Survival of the Inoculated Hosts

Cited by 21 publications

References 17 publications

Antiapoptotic Activity of Autocrine Interleukin-22 and Therapeutic Effects of Interleukin-22-Small Interfering RNA on Human Lung Cancer Xenografts

Antiapoptotic Activity of Autocrine Interleukin-22 and Therapeutic Effects of Interleukin-22-Small Interfering RNA on Human Lung Cancer Xenografts

The IL-20 subfamily of cytokines — from host defence to tissue homeostasis

Interleukin-22 Suppresses the Growth of A498 Renal Cell Carcinoma Cells via Regulation of STAT1 Pathway

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