Potential therapeutic implications of IL-6/IL-6R/gp130-targeting agents in breast cancer

Heo, Tae‐Hwe; Wahler, J.; Suh, Nanjoo

doi:10.18632/oncotarget.7102

Cited by 110 publications

(94 citation statements)

References 100 publications

(113 reference statements)

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“…(40)(41)(42) Previous papers revealed that IL-6 promotes growth and epithelial-mesenchymal transition of CD133 + cells of nonsmall cell lung cancer, (48) tumorigenicity of oral cancer stem cells, (49) cell adhesion, cancer stem-like and metastatic spread of prostate tumors, (50) the growth and metastasis of breast cancer cells, renewal of breast cancer stem cells (BCSC), and drug resistance of BCSC. (51) Furthermore, it was reported that CD133 + cells produced IL-6, (48) suggesting that cancer stem cells may potentially reduce anti-tumor immunity in vivo.…”

Section: Other Aspects Of Interleukin-6 For Anti-tumor Immunity and Tmentioning

confidence: 99%

Interleukin‐6/STAT3 signaling as a promising target to improve the efficacy of cancer immunotherapy

et al. 2017

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Overcoming the immunosuppressive state in tumor microenvironments is a critical issue for improving the efficacy of cancer immunotherapy. Interleukin (IL)‐6, a pleiotropic cytokine, is highly produced in the tumor‐bearing host. Previous studies have indicated that IL‐6 suppresses the antigen presentation ability of dendritic cells (DC) through activation of signal transducer and activator of transcription 3 (STAT3). Thus, we focused on the precise effect of the IL‐6/STAT3 signaling cascade on human DC and the subsequent induction of antitumor T cell immune responses. Tumor‐infiltrating CD11b+ CD11c+ cells isolated from colorectal cancer tissues showed strong induction of the IL‐6 gene, downregulated surface expression of human leukocyte antigen (HLA)‐DR, and an attenuated T cell‐stimulating ability compared with those from peripheral blood mononuclear cells, suggesting that the tumor microenvironment suppresses antitumor effector cells. In vitro experiments revealed that IL‐6‐mediated STAT3 activation reduced surface expression of HLA‐DR on CD14+ monocyte‐derived DC. Moreover, we confirmed that cyclooxygenase 2, lysosome protease and arginase activities were involved in the IL‐6‐mediated downregulation of the surface expression levels of HLA class II on human DC. These findings suggest that IL‐6‐mediated STAT3 activation in the tumor microenvironment inhibits functional maturation of DC to activate effector T cells, blocking introduction of antitumor immunity in cancers. Therefore, we propose in this review that blockade of the IL‐6/STAT3 signaling pathway and target molecules in DC may be a promising strategy to improve the efficacy of immunotherapies for cancer patients.

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Section: Other Aspects Of Interleukin-6 For Anti-tumor Immunity and Tmentioning

confidence: 99%

Interleukin‐6/STAT3 signaling as a promising target to improve the efficacy of cancer immunotherapy

et al. 2017

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“…It has been identified to play noteworthy role in anti-inflammatory, hepatoprotective and antiallergic activities. It suppresses cell proliferation of various types of cancer, including multiple myeloma (13), colon (14), breast (15), pancreatic (16) and prostate cancer (17) by inhibiting the STAT3 signaling pathway. It has not been reported previously that UA inhibits phosphorylation of JAK2 and STAT3 in liver cancer cell lines and suppresses growth of hepatocellular carcinoma.…”

Section: Inhibition Of Stat3 Signaling Pathway By Ursolic Acid Supprementioning

confidence: 99%

Inhibition of STAT3 signaling pathway by ursolic acid suppresses growth of hepatocellular carcinoma

Liu

Shi

et al. 2017

International Journal of Oncology

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The signal transducer and activator of transcription 3 (STAT3) has been found to be constitutively active in liver cancer. There is no STAT3 inhibitors approved to be used clinically for the treatment or prevention of liver cancer. Some dietary compounds including ursolic acid (UA) have been reported to inhibit the growth of cancer cells. However, whether UA could inhibit STAT3 phosphorylation in hepatocellular carcinoma has not been reported. The inhibitory effects of UA on STAT3 phosphorylation, along with cell viability, migration, colony formation in vitro, as well as tumor growth in vivo were examined in human liver cancer cell lines. Our data showed that UA inhibited the P-STAT3 induced by interleukin-6 (IL-6) in Hep3B liver cancer cells which express very low basal level of P-STAT3. The constitutive STAT3 phosphorylation was also inhibited by UA in HEPG2, 7721 and Huh7 human liver cancer cell lines. UA decreased the expression of downstream target genes of STAT3, such as Bcl-2, Bcl-xl and survivin in general, with difference in these cell lines. UA also suppressed cell viability, cell migration and colony formation in liver cancer cells. Furthermore, UA suppressed STAT3 phosphorylation and HEPG2 tumor growth by oral daily treatment in vivo. UA, which exists widely in fruits and herbs, could inhibit STAT3 activation and the growth of human liver cancer cells in vitro and in vivo. It might be a potential health care product that could be used daily for prevention, as well as a promising candidate for chemotherapy of liver cancer.

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“…Thus, IL-6 plays a crucial role in the infl ammation-mediated "cancers types", including prostate, breast, gastric, colon, lung and brain due to inducing different cytoplasmic tyrosine kinases and transcription factors and thus, overexpression of IL-6 is associated with poor prognosis in many cancers. Previous studies mentioned that IL-6 mediated STAT3 activation could be a therapeutic target in gastric, glioblastoma, breast, ovarian and lung cancer patients due to mediating muscle wasting (14)(15)(16)(17)(18)(19)(20). However, further studies are still needed to clarify the association between the changes in IL-6 and STAT-3 levels and cancer patients with and without cachexia.…”

Section: Introductionmentioning

confidence: 99%

IL-6 mediated JAK/STAT3 signaling pathway in cancer patients with cachexia

Eskiler¹,

Bezdegümeli²,

Özman³

et al. 2019

BLL

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OBJECTIVES: We investigated the changes in the IL-6 and STAT3 expression levels in cachectic and noncachectic patients with gastric, lung and breast cancer and evaluated the association between IL-6 and STAT3 levels and cancer types in terms of cachexia condition. BACKGROUND: Cancer-associated cachexia, observed in nearly 50-80 % of cancer patients, has drawn attention in advanced patients. IL-6/JAK/STAT pathway plays an essential role in the progression of cancer cachexia through the regulation of the infl ammatory response. METHODS: This study consisted of 48 gastric, breast and lung cancer patients (18 cachectic and 30 noncachectic) and healthy individuals. Total RNA isolation and cDNA synthesis was performed after the collection of blood samples. IL-6 and STAT3 expression levels were analyzed by RT-PCR analysis. RESULTS: Our fi ndings demonstrated that IL-6 mRNA levels considerably increased 19.89 ± 8.25, 5.18 ± 2.81 and 15.33±9.54-fold in gastric, lung and breast cancer patients with cachexia, respectively. Additionally, a 16.67±7.13, 14.21 ± 11.72 and 8.85 ± 3.89-fold increase in the STAT3 expression level was detected in cachectic gastric, lung and breast cancer patients, respectively (p < 0.01). CONCLUSION: STAT3 may be considered as a therapeutic target for cachectic patients with gastric, lung and breast cancer. Furthermore, IL-6 mediates STAT3 activation in cachectic gastric and breast cancer patients (Tab. 5, Fig. 2, Ref. 62).

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Potential therapeutic implications of IL-6/IL-6R/gp130-targeting agents in breast cancer

Cited by 110 publications

References 100 publications

Interleukin‐6/STAT3 signaling as a promising target to improve the efficacy of cancer immunotherapy

Interleukin‐6/STAT3 signaling as a promising target to improve the efficacy of cancer immunotherapy

Inhibition of STAT3 signaling pathway by ursolic acid suppresses growth of hepatocellular carcinoma

IL-6 mediated JAK/STAT3 signaling pathway in cancer patients with cachexia

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