Review
Biochemistry & Molecular Biology
Yu Chen, Yuzhen Ouyang, Zhixin Li, Xiufang Wang, Jian Ma
Summary: S100A8 and S100A9, as Ca2+ binding proteins in the S100 family, have crucial roles in modulating inflammatory responses and inflammation-associated diseases. They participate in multiple signaling pathways in tumor cells and contribute to tumor development, growth, and metastasis. Moreover, they have shown potential as diagnostic or prognostic biomarkers in cancer and have become therapeutic targets. This review focuses on the characteristics of S100A8/A9, S100A9, and S100A8, their interactions with tumor cells and microenvironments, and their clinical applications as biomarkers and therapeutic targets.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Article
Biochemistry & Molecular Biology
Woosol Chris Hong, Da Eun Lee, Hyeon Woong Kang, Myeong Jin Kim, Minsoo Kim, Ju Hyun Kim, Sungsoon Fang, Hyo Jung Kim, Joon Seong Park
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly form of pancreatic cancer and the role of CD74 in PDAC is not well understood. Silencing CD74 in the pancreatic cancer cell line Capan-1 led to reduced cell proliferation, migration, invasion, increased apoptosis, and decreased expression and secretion of S100A8 and S100A9. The study suggests that CD74 may serve as a potential diagnostic biomarker and therapeutic target for pancreatic cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Ruisheng Song, Kevin Struhl
Summary: The study reveals that the calcium-dependent cytokines S100A8 and S100A9 can act as transcriptional coactivators in breast cellular transformation, enhancing oncogenic transcription and promoting the transformation phenotype.
Review
Immunology
Pengpeng Xia, Xingduo Ji, Li Yan, Siqi Lian, Ziyue Chen, Yi Luo
Summary: S100 proteins are small proteins that are only expressed in vertebrates and play a crucial role in various biological processes. Among them, S100A8, S100A9, and S100A12 are important in resisting microbial infection and maintaining immune homeostasis. They can chelate metal nutrients of pathogens, inhibit pathogen growth, initiate inflammatory signal transduction, induce cytokine expression, and participate in immune regulation. They can also serve as disease markers for screening and detecting related diseases.
Article
Oncology
Wei-Chih Liao, Chih-Ta Chen, You-Shu Tsai, Xin-Ya Wang, Yen-Tzu Chang, Ming-Shiang Wu, Lu-Ping Chow
Summary: Background: Cancer cachexia is a common syndrome in pancreatic cancer patients, characterized by weight loss and muscle wasting. Through bioinformatic analysis, we identified potential pro-inflammatory factors associated with cachexia and investigated their ability to induce muscle atrophy. The expression levels of these factors were significantly elevated in tumors and serum of patients with cachexia compared to those without. Serum levels of these factors were positively correlated with weight loss and could independently predict the occurrence of cachexia.
Review
Biochemistry & Molecular Biology
Farnaz Razmkhah, Sena Kim, Sora Lim, Abdul-Jalil Dania, Jaebok Choi
Summary: S100A8 and S100A9 can initiate various signaling pathways and modulate cell function both inside and outside immune cells. They have been reported as dysregulated genes and proteins in various cancers, including hematologic malignancies. In this review, we discuss their critical roles in forming and promoting the malignant bone marrow microenvironment, as well as their potential as biomarkers and therapeutic targets in hematologic malignancies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Julie Mondet, Simon Chevalier, Pascal Mossuz
Summary: Deregulations of S100A8 and S100A9 genes/proteins in acute leukemias impact prognosis by affecting leukemic cell viability through various mechanisms. Therapeutic targeting of S100A8 and S100A9 shows promise in improving treatment efficiency.
Article
Biochemistry & Molecular Biology
Eva Peterova, Jan Bures, Paula Moravkova, Darina Kohoutova
Summary: The study assessed tissue mRNA encoding different S100 proteins in patients with colorectal adenoma, finding significant differences in mRNA expression levels between healthy mucosa and adenomatous tissue, indicating a potential role of S100 proteins in colorectal cancer formation.
Article
Oncology
Tobias Mohr, Anabel Zwick, Muriel Charlotte Hans, Isabelle Ariane Bley, Felix Leon Braun, Oybek Khalmurzaev, Vsevolod Borisovich Matveev, Philine Loertzer, Alexey Pryalukhin, Arndt Hartmann, Carol-Immanuel Geppert, Hagen Loertzer, Heiko Wunderlich, Carsten Maik Naumann, Holger Kalthoff, Kerstin Junker, Sigrun Smola, Stefan Lohse
Summary: Currently, there are no recommended biomarkers for the routine diagnosis of penile carcinoma (PeCa). However, the rising incidence of this HPV-related cancer highlights the need for potential biomarkers. This study investigated the expression of Calprotectin subunits S100A8 and S100A9, as well as their receptor CD147, in PeCa specimens. The researchers found that an elevated expression of S100A8 and S100A9, along with a positive HPV status, was associated with a higher risk of metastasis. Additionally, an elevated expression of CD147 in HPV-positive PeCa cell lines was correlated with reduced susceptibility to neutrophil-mediated tumor cell killing. Stratifying patients based on their HPV/S100A8/S100A9/CD15/CD147 profile could help identify those with progressing cancer and guide immunotherapeutic treatment strategies.
FRONTIERS IN ONCOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Antonella Russo, Hendrik Schuermann, Matthias Brandt, Katja Scholz, Anna Livia L. Matos, David Grill, Julian Revenstorff, Max Rembrink, Meike von Wulffen, Lena Fischer-Riepe, Peter J. Hanley, Hans Haecker, Monika Pruenster, Francisco Sanchez-Madrid, Sven Hermann, Luisa Klotz, Volker Gerke, Timo Betz, Thomas Vogl, Johannes Roth
Summary: It has been demonstrated that S100A8/S100A9 tetramers can weaken the inflammatory response of leukocytes in vitro and in vivo, and this is mediated by the interaction between S100A8/S100A9 tetramers and CD69, rather than the binding of S100A8/S100A9 dimers to TLR4. These findings reveal the important role of the quaternary structure of S100 proteins in regulating leukocyte inflammatory responses.
Review
Immunology
Jose Inciarte-Mundo, Beatriz Frade-Sosa, Raimon Sanmarti
Summary: S100A9/S100A8 (calprotectin), a member of the S100 protein family, plays a crucial role in innate immunity activation and is essential in the pathogenesis of rheumatoid arthritis (RA). Calprotectin levels in serum or plasma have been found to correlate better with composite inflammatory disease activity indexes compared to conventional markers like C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR). It independently predicts radiographic progression and shows strong correlations with other sensitive techniques to detect inflammation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Xiaoyu Pan, Lin Yang, Shuqi Wang, Yanhui Liu, Lin Yue, Shuchun Chen
Summary: Obesity, driven by inflammation and oxidative stress, increases the risk of cardiovascular disease. This study used single-cell transcriptomics to investigate the mechanism of obesity-induced myocardial damage and the protective effects of semaglutide. The research found that semaglutide reduced inflammation and oxidative stress in obese mice by inhibiting the expression of certain genes in neutrophils, leading to decreased body weight and cardiac damage.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Biology
Saskia-Larissa Jauch-Speer, Marisol Herrera-Rivero, Nadine Ludwig, Bruna Caroline Veras De Carvalho, Leonie Martens, Jonas Wolf, Achmet Imam Chasan, Anika Witten, Birgit Markus, Bernhard Schieffer, Thomas Vogl, Jan Rossaint, Monika Stoll, Johannes Roth, Olesja Fehler
Summary: This study identified C/EBP delta as a new regulator of S100a8 and S100a9 expression and demonstrated its regulatory effects on inflammation. The study also revealed the regulatory mechanisms of C/EBP delta on S100a8 and S100a9 expression and its association with subpopulations of human monocytes in cardiovascular patients.
Article
Biochemistry & Molecular Biology
Marc Wolf, Robiya Joseph, Judith Austermann, Chiara Scharrnbeck-Davis, Sven Hermann, Johannes Roth, Thomas Vogl
Summary: Immune reactions involve the migration of phagocytes to sites of inflammation to prevent uncontrolled extravasation. The calcium-binding protein complex S100A8/S100A9 has both extracellular and intracellular functions, and this study reveals that it plays an important role in coordinating cytoskeleton rearrangement during cell migration. Cells lacking S100A8/S100A9 showed abnormalities in adhesion and motility, as well as dysregulated integrin-mediated adhesion and migration. The findings suggest that intracellular S100A8/S100A9 is involved in a regulatory mechanism that controls the transition between quiescent and activated states of phagocytes.
Article
Immunology
Carolin Christmann, Stefanie Zenker, Leonie Martens, Janina Hubner, Karin Loser, Thomas Vogl, Johannes Roth
Summary: Psoriasis, characterized by altered differentiation of keratinocytes, involves an inflammatory response mediated by S100A8 and S100A9. While the induction of S100-alarmins is associated with increased expression of specific cytokines, the deletion of S100A9 in mice reduces the inflammatory phenotype. However, the expression of S100A8 and S100A9 does not significantly affect the maturation or inflammatory response of keratinocytes, indicating their role in the inflammatory response of keratinocytes during psoriasis.
FRONTIERS IN IMMUNOLOGY
(2021)