IL-33 acts as a foe to MIA PaCa-2 pancreatic cancer

Fang, Yujiang; Zhao, Lei; Xiao, Hualiang; Cook, Kathryn M.; Bai, Qian; Herrick, Elizabeth; Chen, Xuhui; Qin, Chenglu; Zhu, Ziwen; Wakefield, Mark R.; Nicholl, Michael B.

doi:10.1007/s12032-016-0880-3

Cited by 25 publications

(54 citation statements)

References 50 publications

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“…IL-33 has been identified as a useful biomarker in the diagnosis or prediction of prognosis in non-small cell lung cancer (11). Interestingly, other studies have suggested that IL-33 has an anti-tumor effect in colon cancer (12,13) and our previous study on pancreatic and colon cancer echoes these findings (14). This suggests the complex role of IL-33 in the pathogenesis of neoplasia.…”

Section: Introductionsupporting

confidence: 68%

Association between interleukin‑33 and ovarian cancer

et al. 2018

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Ovarian cancer is the leading cause of cancerassociated mortality in the female reproductive system. Interleukin (IL)-33 and its receptor IL 1 receptor like 1 (also termed ST2) are expressed by many cell types including epithelial cells. The role of IL-33 in the pathogenesis of neoplasia remains controversial. The authors previously demonstrated that IL-33 inhibits the growth of pancreatic cancer cells. The present study was performed to explore if IL-33 has any direct effects on ovarian cancer cells. A clonogenic survival assay, immunohistochemistry (IHC), proliferation kit and caspase-3 activity kit were all used to evaluate the direct effects of IL-33 on cell proliferation and apoptosis of a widely studied ovarian cancer cell line, A2780. The possible molecular mechanisms were further evaluated with reverse transcription-polymerase chain reaction and IHC. It was demonstrated that the percentage of colonies and the optical density value of cancer cells were all increased in the presence of IL-33; however, the relative caspase-3 activity in cancer cells was decreased in the presence of IL-33. Molecular mechanism studies revealed that the pro-proliferative effect of IL-33 on cancer cells was associated with decreased levels of p27, and the anti-apoptotic effect of IL-33 was associated with levels of Fas cell surface death receptor (Fas) and tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAILR1). Therefore, IL-33 promoted proliferation and inhibited apoptosis of ovarian cancer cells by downregulation of p27, Fas and TRAILR1. Contrary to previous studies demonstrating an anti-tumor effort in pancreatic cancer, the results of the present study indicated that IL-33 exhibited a significant onco-promoting effect on ovarian cancer. Accordingly, the inhibition of IL-33 may be a promising therapeutic strategy for ovarian cancer.

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Section: Introductionsupporting

confidence: 68%

Association between interleukin‑33 and ovarian cancer

et al. 2018

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“…This indicates that the role of IL-33 in neoplasia is complex and further studies are required to address the exact role of IL-33 in different cancer types. Previously published data demonstrated that IL-33 inhibited proliferation and induced apoptosis of pancreatic cancer cells, and laid the groundwork for the present study ( 12 ).…”

Section: Introductionmentioning

confidence: 72%

IL‑33 notably inhibits the growth of colon cancer cells

Chen

Timko

et al. 2018

Oncol Lett

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Interleukin-33 (IL-33), a damage-associated molecular pattern molecule, is a cytokine within the IL-1 interleukin family that binds to the plasma membrane receptor suppression of tumorigenicity 2 on numerous cell types. IL-33 has been extensively studied in its role in autoimmune diseases, host responses to pathogens and allergens, and has been associated with tumorigenic effects in cancer research. The present study was performed to investigate the effects of IL-33 on colon cancer cells, based off the previous data that have demonstrated an anti-tumor effect of IL-33 on pancreatic cancer cells. The effects of IL-33 on proliferation, cell survival and apoptosis on human HCT-116 colon cancer cells were examined using clonogenic survival assays, proliferation and caspase-3 activity kits, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining and immunocytochemistry. It was determined that the HCT-116 cells demonstrated an notable decrease in optical density value upon incubation with IL-33, along with a decrease in the number of colonies, compared with the controls. It was further determined that the anti-proliferative effect of IL-33 on HCT-116 cells was associated with downregulation of the pro-proliferative molecules cyclin B, cyclin D and cyclin dependent kinase 2. An apoptosis-inducing effect of IL-33 on HCT-116 cells was associated with downregulation of the anti-apoptotic molecules Flice-like inhibitory protein and B-cell lymphoma 2. Taken together, the results indicated that IL-33 inhibits the growth of colon cancer by suppressing cellular proliferation, whilst simultaneously promoting apoptosis.

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“…ST2 also has a significant effect on the pathogenesis of several diseases, including inflammation, allergies, fibrillation, cardiac hypertrophy and rheumatoid arthritis (22). Numerous studies have suggested that ST2 expression is associated with carcinogenesis and tumor progression in multiple cancer types (13)(14)(15)(16)22). ST2 has been shown to regulate innate and acquired immunity in tumors.…”

Section: Discussionmentioning

confidence: 99%

“…It has also been suggested that ST2L/IL-33 participates in a number of inflammatory immune response processes associated with asthma, allergic diseases, autoimmune diseases, cardiovascular diseases and other conditions associated with acute heart failure, myocardial infarction, respiratory failure and acute trauma (11,12). Previous studies revealed that ST2 was involved in the pathogenesis and prognosis of multiple types of cancer, including glioblastoma, breast and pancreatic cancer, and leukemia (13)(14)(15)(16). However, to the best of our knowledge, the role of ST2 in gastric cancer remains to be elucidated.…”

Section: Decreased St2 Expression Is Associated With Gastric Cancer Pmentioning

confidence: 99%

Decreased ST2 expression is associated with gastric cancer progression and pathogenesis

Bai

You

et al. 2019

Oncol Lett

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Gastric cancer is a type of cancer with increasing incidence and high mortality rates, but molecular biomarkers of diagnostic and therapeutic value are currently lacking. The aim of the present study was to examine the expression pattern of the interleukin 1 receptor-like 1 (ST2) protein and assess its clinicopathological significance in gastric cancer. Western blot analysis of 12 gastric cancer specimens and paired adjacent tissues demonstrated that the protein levels of 2 isoforms of ST2, soluble secreted ST2 and the ST2 variant without the third immunoglobulin motif and splicing in the C-terminal, were markedly decreased in cancer tissues compared with non-cancerous tissues. Immunohistochemical analysis demonstrated that ST2 protein expression was markedly decreased in primary gastric cancer tissues (39.1%, 90/230) compared with adjacent non-cancerous tissues (60.7%, 54/89) (P<0.05). Statistical analysis demonstrated that decreased ST2 expression was significantly associated with advanced tumor node metastasis stage (P<0.001) and tumor differentiation (P<0.001). These data suggest that ST2 protein may be a valuable biomarker of gastric cancer progression and pathogenesis.

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IL-33 acts as a foe to MIA PaCa-2 pancreatic cancer

Cited by 25 publications

References 50 publications

Association between interleukin‑33 and ovarian cancer

Association between interleukin‑33 and ovarian cancer

IL‑33 notably inhibits the growth of colon cancer cells

Decreased ST2 expression is associated with gastric cancer progression and pathogenesis

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