CD44, IL-33, and ST2 Gene Polymorphisms on Hepatocellular Carcinoma Susceptibility in the Chinese Population

Pan, Xiaolan; Li, Meiqin; Huang, Lei; Mo, Dan; Liang, Yucheng; Huang, Zhaodong; Zhu, Bo; Fang, Min

doi:10.1155/2020/2918517

Cited by 3 publications

(3 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, two different polymorphisms in the IL-33 gene have been reported to increase the expression of IL-33 and to be associated with higher risk to develop hepatocellular carcinoma (Wei et al 2019b ; Pan et al 2020 ). Like other factors involved in stemness, IL-33 is also capable of inducing resistance to chemotherapy.…”

Section: Main Textmentioning

confidence: 99%

Macrophages and cancer stem cells: a malevolent alliance

Allavena

Digifico

Belgiovine

2021

Mol Med

View full text Add to dashboard Cite

Myeloid cells infiltrating tumors are gaining ever growing attention in the last years because their pro-tumor and immunosuppressive functions are relevant for disease progression and therapeutic responses. The functional ambiguity of tumor-associated macrophages (TAMs), mostly promoting tumor evolution, is a challenging hurdle. This is even more evident in the case of cancer stem cells (CSCs); as active participants in the specialized environment of the cancer stem cell niche, TAMs initiate a reciprocal conversation with CSCs. TAMs contribute to protect CSCs from the hostile environment (exogenous insults, toxic compounds, attacks from the immune cells), and produce several biologically active mediators that modulate crucial developmental pathways that sustain cancer cell stemness. In this review, we have focused our attention on the interaction between TAMs and CSCs; we describe how TAMs impact on CSC biology and, in turn, how CSCs exploit the tissue trophic activity of macrophages to survive and progress. Since CSCs are responsible for therapy resistance and tumor recurrence, they are important therapeutic targets. In view of the recent success in oncology obtained by stimulating the immune system, we discuss some macrophage-targeted therapeutic strategies that may also affect the CSCs and interrupt their malevolent alliance.

show abstract

Section: Main Textmentioning

confidence: 99%

Macrophages and cancer stem cells: a malevolent alliance

Allavena

Digifico

Belgiovine

2021

Mol Med

View full text Add to dashboard Cite

show abstract

“…Cluster of differentiation 44 (CD44) is a multifunctional transmembrane receptor expressed on various cell types, with ligand binding activating intracellular signalling pathways to stimulate cytokine release and lymphocyte activation [ 20 ]. The CD44 rs187115 T > C SNP is located within intron 1, with the C allele reportedly associated with a higher risk of HBV-HCC development in Taiwan and China [ 21 , 55 ]. The mechanisms are yet to be determined, but a role in the p53 stress response has been proposed [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

A PDCD1 Role in the Genetic Predisposition to NAFLD-HCC?

Eldafashi

Darlay

Shukla

et al. 2021

Cancers

View full text Add to dashboard Cite

Obesity and non-alcoholic fatty liver disease (NAFLD) are contributing to the global rise in deaths from hepatocellular carcinoma (HCC). The pathogenesis of NAFLD-HCC is not well understood. The severity of hepatic steatosis, steatohepatitis and fibrosis are key pathogenic mechanisms, but animal studies suggest altered immune responses are also involved. Genetic studies have so far highlighted a major role of gene variants promoting fat deposition in the liver (PNPLA3 rs738409; TM6SF2 rs58542926). Here, we have considered single-nucleotide polymorphisms (SNPs) in candidate immunoregulatory genes (MICA rs2596542; CD44 rs187115; PDCD1 rs7421861 and rs10204525), in 594 patients with NAFLD and 391 with NAFLD-HCC, from three European centres. Associations between age, body mass index, diabetes, cirrhosis and SNPs with HCC development were explored. PNPLA3 and TM6SF2 SNPs were associated with both progression to cirrhosis and NAFLD-HCC development, while PDCD1 SNPs were specifically associated with NAFLD-HCC risk, regardless of cirrhosis. PDCD1 rs7421861 was independently associated with NAFLD-HCC development, while PDCD1 rs10204525 acquired significance after adjusting for other risks, being most notable in the smaller numbers of women with NAFLD-HCC. The study highlights the potential impact of inter individual variation in immune tolerance induction in patients with NAFLD, both in the presence and absence of cirrhosis.

show abstract

“…Numerous studies have demonstrated that IL-33 plays dual roles regulating tumor transformation, growth, and metastasis in many cancers, including non-small cell lung cancer (NSCLC), colorectal cancer, gastric cancer, pancreatic tumor, and breast cancer by directly acting on tumor cells or by indirectly affecting immune cells or the tumor microenvironment [ 219 , 220 , 221 , 222 , 223 , 224 ]. In some populations of China, individuals with at least one C allele of ST2 rs3821204 exhibited a higher risk of hepatocellular carcinoma compared to those with GG genes [ 225 ]. Patients with NSCLC in their peripheral blood exhibited increased IL-33 levels in serum and plasma, while IL-33 levels in plasma were decreased with disease progression [ 226 , 227 ].…”

Section: Il-33 and Immune-related Diseasesmentioning

confidence: 99%

Dual Immune Regulatory Roles of Interleukin-33 in Pathological Conditions

Guo

Bossila

et al. 2022

Cells

View full text Add to dashboard Cite

Interleukin-33 (IL-33), a member of the IL-1 cytokine family and a multifunctional cytokine, plays critical roles in maintaining host homeostasis and in pathological conditions, such as allergy, infectious diseases, and cancer, by acting on multiple types of immune cells and promoting type 1 and 2 immune responses. IL-33 is rapidly released by immune and non-immune cells upon stimulation by stress, acting as an “alarmin” by binding to its receptor, suppression of tumorigenicity 2 (ST2), to trigger downstream signaling pathways and activate inflammatory and immune responses. It has been recognized that IL-33 displays dual-functioning immune regulatory effects in many diseases and has both pro- and anti-tumorigenic effects, likely depending on its primary target cells, IL-33/sST2 expression levels, cellular context, and the cytokine microenvironment. Herein, we summarize our current understanding of the biological functions of IL-33 and its roles in the pathogenesis of various conditions, including inflammatory and autoimmune diseases, infections, cancers, and cases of organ transplantation. We emphasize the nature of context-dependent dual immune regulatory functions of IL-33 in many cells and diseases and review systemic studies to understand the distinct roles of IL-33 in different cells, which is essential to the development of more effective diagnoses and therapeutic approaches for IL-33-related diseases.

show abstract

CD44, IL-33, and ST2 Gene Polymorphisms on Hepatocellular Carcinoma Susceptibility in the Chinese Population

Cited by 3 publications

References 53 publications

Macrophages and cancer stem cells: a malevolent alliance

Macrophages and cancer stem cells: a malevolent alliance

A PDCD1 Role in the Genetic Predisposition to NAFLD-HCC?

Dual Immune Regulatory Roles of Interleukin-33 in Pathological Conditions

Contact Info

Product

Resources

About