Interleukin-11 is a Marker for Both Cancer- and Inflammation-Associated Fibroblasts that Contribute to Colorectal Cancer Progression

Nishina, Takashi; Deguchi, Yutaka; Takeda, Wakami; Ohtsuka, Masato; Ohshima, Daisuke; Yamazaki, Soh; Kawauchi, Mika; Nakamura, Eri; Nishiyama, Chiharu; Kojima, Yuko; Adachi‐Akahane, Satomi; Hasegawa, Mizuho; Nakayama, Mizuho; Oshima, Masanobu; Yagita, Hideo; Shibuya, Kazutoshi; Mikami, Taisei; Inohara, Naohiro; Tada, Norio; Nakano, Hiroyasu

doi:10.1101/2020.01.25.919795

Cited by 2 publications

(3 citation statements)

References 49 publications

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“…This hypothesis is further supported by several other mammalian studies that have reported a proregenerative role for the components of IL-6 family/STAT3 signaling after tissue damage (27,(63)(64)(65)(66). Furthermore, in the zebrafish heart, we found that endocardial Stat3 activation after injury depended on Il-11 signaling, while in mammals, it was reported that stimulation with IL-11 only resulted in a transient Stat3 activation for various cell types in vitro (67,68). This hypothesis may explain in part why nonregenerative species do not form a blastema after injury, but in contrast predominantly display myofibroblast activation and scar formation, highlighting the need for a deeper comparative investigation of the mechanisms downstream of IL11RA/Il11ra activation in regenerative and nonregenerative species.…”

Section: Discussionsupporting

confidence: 89%

Interleukin-11 signaling promotes cellular reprogramming and limits fibrotic scarring during tissue regeneration

et al. 2021

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Damage-induced fibrotic scarring limits tissue regeneration in mammals and is a leading cause of morbidity. In contrast, species like zebrafish can regenerate damaged tissues without excessive fibrosis. However, whether specific signaling pathways can both limit fibrosis and promote regeneration is unclear. Here, we show that interleukin-11 (Il-11)/Stat3 signaling has such a dual function. Zebrafish lacking Il-11 receptor function display severely compromised heart, fin, and scale regeneration. Deep phenotyping and transcriptional analysis of adult hearts and fins show that Il-11 signaling drives cellular reprogramming to orchestrate global and tissue-specific regenerative programs and broadly antagonizes hallmarks of adult mammalian scarring. Mechanistically, our data indicate that IL-11 signaling in endothelial cells antagonizes profibrotic transforming growth factor- signaling and endothelial-to-mesenchymal transition, limiting scarring and promoting cardiomyocyte repopulation, after injury. Overall, our findings position damage-induced Il-11/Stat3 signaling in a key role limiting fibrosis and promoting regeneration, revealing novel targets for regenerative therapies.

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Section: Discussionsupporting

confidence: 89%

Interleukin-11 signaling promotes cellular reprogramming and limits fibrotic scarring during tissue regeneration

et al. 2021

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“…While mild UC patient's exhibit increased IL-11 expression, severe UC patients show a decrease in expression [277]. A study using a human cancer database found that genes enriched in IL-11+ fibroblasts were elevated in human colorectal cancer, and the high expressions of several of these genes correlated with a reduced disease-free survival rate in colorectal cancer patients [278]. Previous studies have demonstrated that IL-11+ cells are derived from stromal or epithelial cells [53,158].…”

Section: Interleukin-11mentioning

confidence: 99%

“…There is substantial evidence that IL-11 regulates tumor progression, cellular growth, and differentiation. While IL-11 has been suggested to become a therapeutically important molecule in the supportive care of cancer patients receiving chemotherapy [278], the study indicates that IL-11 may upregulate colorectal carcinoma cell growth and/or invasion, necessitating cautious attention to the therapeutic use of IL-11 [279]. Table 3 contains detailed description of interleukin families involved in CRC and their potential therapeutic strategies.…”

Section: Interleukin-11mentioning

confidence: 99%

Interleukins (Cytokines) as Biomarkers in Colorectal Cancer: Progression, Detection, and Monitoring

Maryam

Krukiewicz

Haq

et al. 2023

JCM

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Cancer is the primary cause of death in economically developed countries and the second leading cause in developing countries. Colorectal cancer (CRC) is the third most common cause of cancer-related deaths worldwide. Risk factors for CRC include obesity, a diet low in fruits and vegetables, physical inactivity, and smoking. CRC has a poor prognosis, and there is a critical need for new diagnostic and prognostic biomarkers to reduce related deaths. Recently, studies have focused more on molecular testing to guide targeted treatments for CRC patients. The most crucial feature of activated immune cells is the production and release of growth factors and cytokines that modulate the inflammatory conditions in tumor tissues. The cytokine network is valuable for the prognosis and pathogenesis of colorectal cancer as they can aid in the cost-effective and non-invasive detection of cancer. A large number of interleukins (IL) released by the immune system at various stages of CRC can act as “biomarkers”. They play diverse functions in colorectal cancer, and include IL-4, IL-6, IL-8, IL-11, IL-17A, IL-22, IL-23, IL-33, TNF, TGF-β, and vascular endothelial growth factor (VEGF), which are pro-tumorigenic genes. However, there are an inadequate number of studies in this area considering its correlation with cytokine profiles that are clinically useful in diagnosing cancer. A better understanding of cytokine levels to establish diagnostic pathways entails an understanding of cytokine interactions and the regulation of their various biochemical signaling pathways in healthy individuals. This review provides a comprehensive summary of some interleukins as immunological biomarkers of CRC.

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Interleukin-11 is a Marker for Both Cancer- and Inflammation-Associated Fibroblasts that Contribute to Colorectal Cancer Progression

Cited by 2 publications

References 49 publications

Interleukin-11 signaling promotes cellular reprogramming and limits fibrotic scarring during tissue regeneration

Interleukin-11 signaling promotes cellular reprogramming and limits fibrotic scarring during tissue regeneration

Interleukins (Cytokines) as Biomarkers in Colorectal Cancer: Progression, Detection, and Monitoring

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