Pathogenic Roles of S100A8 and S100A9 Proteins in Acute Myeloid and Lymphoid Leukemia: Clinical and Therapeutic Impacts

Mondet, Julie; Chevalier, Simon; Mossuz, Pascal

doi:10.3390/molecules26051323

Cited by 43 publications

(52 citation statements)

References 78 publications

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“…Araki et al also illustrated that the receptor for advanced glycation end products (RAGE) is one of the major S100A8/A9 receptors, which results in the activation of NF κ B [ 49 ]. Moreover, biologic effects of S100A8/9 via both RAGE and TLR4 on hematopoietic stem cells are by excretion of proinflammatory cytokines in the hematological process [ 50 ]. Furthermore, S100A8 and S100A9 induced activation of p38 MAPK signaling was blocked by the toll-like receptor 4 (TLR4) inhibitor [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

S100A8/A9 Molecular Complexes Promote Cancer Migration and Invasion via the p38 MAPK Pathway in Nasopharyngeal Carcinoma

Zhang

Huang³

et al. 2021

Bioinorganic Chemistry and Applications

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Nasopharyngeal carcinoma (NPC) is one type of malignancy associated with migration and invasion through a currently unclear mechanism. We previously discovered S100A8/A9 levels were roughly elevated in the plasma of NPC patients as the promising biomarkers. However, their expressions and underlying functions in NPC tissues are still unknown. In the present study, we analyzed 49 NPC tissues and 20 chronic pharyngitis (CP) tissues. Immunohistochemical staining was performed in different tissues and analyzed by the Mann–Whitney U test statistically. Transwell migration and invasion experiments were further performed to determine S100A8/A9 effects on NPC. Our results showed that S100A8/A9 in NPC tissues were significantly higher than those in CP tissues, closely associated with NPC clinical stages. Intriguingly, exogenous S100A8/A9 protein stimulation could dramatically enhance NPC migration and invasion abilities. In addition, p38 MAPK pathway blockade could diminish the migration and invasion of NPC cells stimulated by S100A8/A9 proteins. The downstream tumor invasion and migration associated proteins (e.g., MMP7) were also elevated in NPC tissues, consistent with S100A8/A9 overexpression. Taken together, our present findings suggest that the secreted soluble inflammatory factors S100A8/A9 might promote cancer migration and invasion via the p38 MAPK signaling pathway along with invasion/migration associated proteins overexpression in the tumor microenvironment of NPC. This may shed light on the mechanism understanding of NPC prognosis and provide more novel clues for NPC diagnosis and therapy.

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Section: Discussionmentioning

confidence: 99%

S100A8/A9 Molecular Complexes Promote Cancer Migration and Invasion via the p38 MAPK Pathway in Nasopharyngeal Carcinoma

Zhang

Huang³

et al. 2021

Bioinorganic Chemistry and Applications

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“…S100A8/S100A9 (also called calprotectin) has both intercellular and extracellular functions. Upregulation of S100A8 and S100A9 occurs in various human cancer types and may participate in tumor growth, metastasis, angiogenesis and immune evasion Ichikawa et al, 2011;Grebhardt et al, 2014;Goh et al, 2017;Mondet et al, 2021). Elevated expression of S100A8/S100A9 caused glucocorticoid resistance in MLL rearranged infant acute lymphoid leukemia (Spijkers-Hagelstein et al, 2012) and negatively associated with BCL2 inhibitor venetoclax in AML (Karjalainen et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

S100 Calcium Binding Protein Family Members Associate With Poor Patient Outcome and Response to Proteasome Inhibition in Multiple Myeloma

Liu

Wang

Miettinen

et al. 2021

Front. Cell Dev. Biol.

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Despite several new therapeutic options, multiple myeloma (MM) patients experience multiple relapses and inevitably become refractory to treatment. Insights into drug resistance mechanisms may lead to the development of novel treatment strategies. The S100 family is comprised of 21 calcium binding protein members with 17 S100 genes located in the 1q21 region, which is commonly amplified in MM. Dysregulated expression of S100 family members is associated with tumor initiation, progression and inflammation. However, the relationship between the S100 family and MM pathogenesis and drug response is unknown. In this study, the roles of S100 members were systematically studied at the copy number, transcriptional and protein level with patients’ survival and drug response. Copy number analysis revealed a predominant pattern of gains occurring in S100 genes clustering in the 1q21 locus. In general, gains of genes encoding S100 family members associated with worse patient survival. However, S100 gene copy number and S100 gene expression did not necessarily correlate, and high expression of S100A4 associated with poor patient survival. Furthermore, integrated analysis of S100 gene expression and ex vivo drug sensitivity data showed significant negative correlation between expression of S100 family members (S100A8, S100A9, and S100A12) and sensitivity to some drugs used in current MM treatment, including proteasome inhibitors (bortezomib, carfilzomib, and ixazomib) and histone deacetylase inhibitor panobinostat. Combined proteomic and pharmacological data exhibited significant negative association of S100 members (S100A4, S100A8, and S100A9) with proteasome inhibitors and panobinostat. Clinically, the higher expression of S100A4 and S100A10 were significantly linked to shorter progression free survival in patients receiving carfilzomib-based therapy. The results indicate an association and highlight the potential functional importance of S100 members on chromosome 1q21 in the development of MM and resistance to established myeloma drugs, including proteasome inhibitors.

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“…Although S100A9 have been studied in many types of cancers, the biological function in malignancies was still remains contradictory and poorly understood. For example, elevated S100A9 in malignant tissues were associated with significantly shorter cancer survival, while downregulated S100A9 is correlated with tumor proliferation, inflammation invasion and angiogenesis [7][8][9][10][11][12][13]. To our knowledge, this is the first research to investigate the effects of S100A9 in NB patients.…”

Section: Introductionmentioning

confidence: 89%

Identification S100A9 as a potential biomarker in neuroblastoma

et al. 2021

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Background More than half of Neuroblastoma (NB) patients presented with distant metastases and the relapse of metastatic patients was up to 90%. It is urgent to explore a biomarker that could facilitate the prediction of metastasis in NB patients. Methods and results In the present study, we systematically analyzed Gene Expression Omnibus datasets and focused on identifying the critical molecular networks and novel key hub genes implicated in NB metastasis. In total, 176 up-regulated and 19 down-regulated differentially expressed genes (DEGs) were identified. Based on these DEGs, a PPI network composed of 150 nodes and 452 interactions was established. Through PPI network identification combined with qRT-PCR, ELISA and IHC, S100A9 was screened as an outstanding gene. Furthermore, in vitro tumorigenesis assays demonstrated that S100A9 overexpression enhanced the proliferation, migration and invasion of NB cells. Conclusions Taken together, our findings suggested that S100A9 could participate in NB tumorigenesis and progression. In addition, S100A9 has the potential to be used as a promising clinical biomarker in the prediction of NB metastasis.

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Pathogenic Roles of S100A8 and S100A9 Proteins in Acute Myeloid and Lymphoid Leukemia: Clinical and Therapeutic Impacts

Cited by 43 publications

References 78 publications

S100A8/A9 Molecular Complexes Promote Cancer Migration and Invasion via the p38 MAPK Pathway in Nasopharyngeal Carcinoma

S100A8/A9 Molecular Complexes Promote Cancer Migration and Invasion via the p38 MAPK Pathway in Nasopharyngeal Carcinoma

S100 Calcium Binding Protein Family Members Associate With Poor Patient Outcome and Response to Proteasome Inhibition in Multiple Myeloma

Identification S100A9 as a potential biomarker in neuroblastoma

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