Written | 2011-02 | Claus Kerkhoff, Saeid Ghavami |
Dept VAC / IMCI, Helmholtz Centre for Infection Research, Inhoffenstr 7, D-38124 Braunschweig, Germany (CK); Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada (SG) |
Identity |
Alias (NCBI) | 60B8AG | CAGB | CFAG | CGLB | L1AG | LIAG | MAC387 | MIF | MRP14 | NIF | P14 |
HGNC (Hugo) | S100A9 |
HGNC Alias symb | P14 | MIF | NIF | LIAG | MRP14 | MAC387 | 60B8AG | CGLB |
HGNC Previous name | CAGB | CFAG |
HGNC Previous name | calgranulin B | S100 calcium-binding protein A9 (calgranulin B) |
LocusID (NCBI) | 6280 |
Atlas_Id | 45569 |
Location | 1q21.3 [Link to chromosome band 1q21] |
Location_base_pair | Starts at 153357854 and ends at 153361023 bp from pter ( according to GRCh38/hg38-Dec_2013) [Mapping S100A9.png] |
Local_order | Distal to PGLYRP4 peptidoglycan recognition protein 4, proximal to S100A12 (S100 calcium binding protein A12). |
Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
ANKRD11 (16q24.3) / S100A9 (1q21.3) | CCDC12 (3p21.31) / S100A9 (1q21.3) | KRT4 (12q13.13) / S100A9 (1q21.3) | |
MSRA (8p23.1) / S100A9 (1q21.3) | R3HDM4 (19p13.3) / S100A9 (1q21.3) | RBM18 (9q33.2) / S100A9 (1q21.3) | |
S100A9 (1q21.3) / KRT4 (12q13.13) | S100A9 (1q21.3) / VAT1L (16q23.1) |
DNA/RNA |
Note | S100A9 belongs to the S100/calgranulin family of small non-ubiquitous cytoplasmic Ca2+-binding proteins of EF-hand type. The proteins were referred to "S100" because of their solubility in saturated ammonium sulphate solution. Sixteen of 21 members are localised in a cluster on human chromosome 1q21. The clustered organization of these S100 genes is conserved during evolution (Ridinger et al., 1998). A comparison between man and mouse has shown that during evolution, the colinearity of the S100 gene cluster has been destroyed by some inversions. However, the colocalization of the myeloid expressed S100 genes such as S100A8, S100A9, and S100A12 is conserved. It has been speculated, that the structural integrity of that part of the locus is necessary for the coordinated expression of these genes (Nacken et al., 2001). Remarkably, the S100 gene cluster is located in close proximity to a region which has been frequently rearranged in human cancer (Carlsson et al., 2005) and to the epidermal differentiation complex (EDC) (Mischke et al., 1996). EDC is a cluster of genes on chromosome 1q21 encoding proteins that fulfil important functions in terminal differentiation in the human epidermis, including filaggrin, loricrin and others. In addition, linkage analyses have identified a psoriasis susceptibility region, the PSORS4 locus, that is close to the S100 gene cluster (Hardas et al., 1996; Semprini et al., 2002). These data are important indications for the involvement of S100 genes in inflammatory as well as neoplastic disorders. It has been speculated that the rearrangements result in a deregulated expression of S100 genes associated with neoplasia. |
Description | The S100 gene structure has been structurally conserved during evolution. Similar to most S100 genes S100A9 consists of three exons that are separated by two introns. |
Transcription | In the S100A9 gene, exon 1 encodes the untranslated region. The protein is encoded by sequences in exon 2 and exon 3, encoding a N-terminal and a C-terminal EF-hand motif, respectively. The sequence of human S100A9 cDNA has an open reading frame of 352 nucleotides. S100A9 expression appears to be restricted to a specific stage of myeloid differentiation. The protein is present in circulating neutrophils and monocytes, but not in resting tissue macrophages. In peripheral blood monocytes it is down regulated during maturation to macrophages. Despite a number of distinct regulatory regions are located upstream of the transcription initiation site, the corresponding nuclear factors as well as the underlying molecular mechanisms still remain unclear. Transcription factors such as PU.1 (Henkel et al., 2002), C/EBP-alpha and C/EBP-beta (Kuruto-Niwa et al., 1998) have been shown to drive S100 gene expression within the myeloid lineage. For example, during differentiation of HL-60 cells into monocyte-like cells two still not identified factors were found to bind to the upstream regions of S100A9 gene; one adjacent to the TATA box and another in the region between -400 and -150 (Kuwayama et al., 1993). Another study revealed a CCAAT/enhancer binding protein (C/EBP)-binding motif located at position -81 upstream of the S100A9 gene. Both C/EBP-alpha and -beta bind to this motif in a myeloid/monocytic differentiation-dependent manner (Kuruto-Niwa et al., 1998). C/EBP was shown to be alone sufficient to drive S100A9 expression in otherwise negative cells. C/EBP up-regulation is antagonized by myb, a transcription factor active in differentiated myeloid/monocytic cells (Klempt et al., 1998). The presence of distinct epithelial and myeloid-specific regulatory regions upstream of the transcription initiation site has been demonstrated by detailed deletion analysis (Klempt et al., 1999). Besides the very specific action of particular upstream DNA elements, the S100A9 gene contains a potent enhancer, which is harbored within positions 153 to 361 of its first intron (Melkonyan et al., 1998). The functional relevance of this enhancer in S100A9 expression is supported by its conservation in human and murine S100A9 genes at almost identical positions. Promoter analyses revealed a regulatory element within the S100A9 promoter referred to as MRP regulatory element (MRE) that drives the S100A9 gene expression in a cell-specific and differentiation-dependent manner. This regulatory region is located at position -400 to -374 bp, and two distinct nuclear complexes were demonstrated to bind to this region. Interestingly, the formation of the nuclear protein complexes closely correlates with the myeloid-specific expression of the S100A9 gene and, were therefore referred to as MRE-binding complex A (MbcA) and MbcB, respectively. Analysis of one of the two nuclear complexes revealed a heterocomplex consisting of transcriptional intermediary factor 1 beta (TIF1 beta) and a yet unidentified protein with homology to KRAB domain-containing (Kruppel-related) zinc finger proteins (ZFP) (Kerkhoff et al., 2002). Beside its expression in myeloid cells S100A9 is expressed in epithelia under specific conditions. Its expression is transiently induced in keratinocytes after epidermal injury and UVB irradiation, and the protein is expressed at extremely high levels in psoriatic keratinocytes. Furthermore, its expression is induced by pro-inflammatory cytokines such as TNF alpha and IL1 beta. Recently, a complex of Poly (ADP-ribose) polymerase (PARP-1) and Ku70/Ku80 has been demonstrated to drive the stress response-specific S100 gene expression (Grote et al., 2006). The stress response-induced expression of the S100 proteins points to an important role in skin pathology. In breast cancer cells S100A9 gene expression is induced by the cytokine oncostatin M (OM) through the STAT3-signaling cascade (Li et al., 2004). This finding is in accordance with another study showing that IL-22 up-regulates the expression of S100A7, S100A8, and S100A9 in keratinocytes. IL-22 has been demonstrated to induce STAT3 activation in keratinocytes (Boniface et al., 2005). |
Pseudogene | Not known. |
Protein |
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Gene: Box = exon (light blue = 5'UTR, yellow = CDS, red = 3'UTR); Line = intron. Protein: Upper boxes, alternating colours: exons (coding part only). Lower boxes: protein domains. Green box = not structure; blue box = helix; violett box = calcium-binding domain. | |
Description | The sequence of human S100A9 cDNA has an open reading frame of 352 nucleotides predicting a protein of 114 amino acids and a calculated Mr of 13242 Da. Beside the full-length form of S100A9 there is a truncated isoform of S100A9 resulting from alternative translation. The full-length form of S100A9 lacks the first Met, and Thr at position 2 is acetylated leading to a calculated molecular mass of 13154 Da. The N-truncated isoform starts with Met at position 5. Posttranslational removing of Met at position 5 and consequent acetylation of Ser at position 6 leads to a calculated molecular mass of 12690 Da. The theoretical isoelectric point of the full length form is 5.7 and for the truncated form is 5.5, respectively. S100A9 is composed of two helix-loop-helix EF-hand motifs. The C-terminal EF-hand contains a canonical Ca2+-binding loop of 12 amino acids. Conversely, the N-terminal EF-hand contains a Ca2+-binding loop of 14 residues that binds Ca2+ mostly through main-chain carbonyl groups that which is specific to S100 proteins. Consequently, S100 proteins have a weaker Ca2+ affinity than typical Ca2+ sensors such as calmodulin (Donato, 2003). An important posttranslational modification of S100A9 represents the phosphorylation of threonine at position 113. It can be phosphorylated upon PMN activation, and phosphorylation of this residue is specifically regulated by the Ca2+-ionophore, ionomycin. Recent studies give evidence for S100A9 being a p38 MAPK substrate in human neutrophils (Lominadze et al., 2005). This phosphorylation is involved in translocation and functional events. In vivo and in vitro experiments have shown that S100 proteins form homo-, hetero- and oligomeric assemblies (Hunter and Chazin, 1998; Osterloh et al., 1998; Pröpper et al., 1999; Moroz et al., 2003). Together with their specific cell- and tissue-expression patterns, the structural variations, and the different metal ion binding properties (Ca2+, Zn2+ and Cu2+) the S100 protein complexes might be functionally diversified. S100A9 preferentially interacts with S100A8. It is worthwhile mentioning that the murine analogs display a stronger tendency to form homodimeric protein complexes. In view of the formation of different tertiary structures with putative distinct functions it is tempting to speculate that S100A8 and/or A9 have different functions in mouse and man. |
Expression | S100A9 is mainly expressed in cells of the myeloid lineage, however, its gene expression is induced in epithelial cells in response to stress, in specific conditions such as wound healing, UV exposition, abundant in psoriais keratinocytes, differentially expressed in several cancers. |
Localisation | Mostly cytoplasmic, but also at membranes and cytoskeleton. In resting phagocytes the S100A8/A9 protein complex is mainly located in the cytosol. Upon cellular activation the protein complex is either translocated to cytoskeleton and plasma membrane or released into the extracellular environment. The translocation pathways occur upon the elevation of the intracellular calcium level (Roth et al., 1993). At a later time point, the S100A8/A9 heterodimers can be detected on the surface of monocytes (Bhardwaj et al., 1992). The mechanism by which the S100A8/A9 heterodimer penetrates the plasma membrane remains unclear since the S100 proteins lack a transmembrane signaling region. The secretion pathway relies on the activation of protein kinase C. This pathway differs from the classical as well as the alternative secretion pathways of cytokines (Moqbel and Coughlin, 2006). It has been demonstrated that this novel secretion pathway is energy-consuming and depends on an intact microtubule network (Murao et al., 1990; Rammes et al., 1997). Recent investigations give evidence that interaction of S100A8/A9 with annexin-6 is involved in surface expression and release of S100A8/A9 (Bode et al., 2008). Annexins are another class of Ca2+-regulated proteins. They are characterized by the unique architecture of their Ca2+-binding sites, which enables them to peripherally dock onto negatively charged membrane surfaces in their Ca2+-bound conformation. This property links annexins to many membrane-related events such as certain exocytic and endocytic transport steps. This is an interesting finding since S100A8 and S100A9 are expressed in cancerous cells of secretory tissues as breast and prostate. Cells originating from such glandular tissues are rich in membrane structures, suggesting that membrane-associated molecular targets for the S100A8/A9 proteins could be potentially found in these cells. Recent investigations also demonstrated the association of S100A8/A9 with cholesterol-enriched membrane microdomains (lipid rafts) (Nacken et al., 2004). This observation is in agreement with the enhancing effect of S100A8/A9 on NADPH oxidase since the formation of the oxidase complex takes place at lipid rafts. |
Function | Intra- as well as extracellular roles have been proposed for the S100 proteins. Intracellular activities of S100A8/A9 Extracellular activities of S100A8/A9 |
Homology | Overall, the S100 proteins share significant sequential homology in the EF-hand motifs, but are least conserved in the hinge region. This region is proposed to provide for specific interaction with target proteins (Groves et al., 1998; Zimmer et al., 2003; Santamaria-Kisiel et al., 2006; Fernandez-Fernandez et al., 2008; van Dieck et al., 2009). The availability of high-resolution S100-target structures has highlighted important structural features that contribute to S100 protein functional specificity (Bhattacharya et al., 2003). The functional diversification of S100 proteins is achieved by their specific cell- and tissue-expression patterns, structural variations, different metal ion binding properties (Ca2+, Zn2+ and Cu2+) as well as their ability to form homo-, hetero- and oligomeric assemblies (Hunter and Chazin, 1998; Osterloh et al., 1998; Pröpper et al., 1999; Tarabykina et al., 2001; Moroz et al., 2003; Fritz et al., 2010). Although the function of S100 proteins in cancer cells in most cases is still unknown, the specific expression patterns of these proteins are a valuable diagnostic tool. |
Implicated in |
Note | |
Entity | General note |
Note | Comparative and functional genomics have revealed that a number of S100 proteins are found to be differentially expressed in cancer cells. Several of these have been associated with tumor development, cancer invasion or metastasis in recent studies (for review see Salama et al., 2008). S100A8 and S100A9 are abundant in cells of the myeloid lineage, are released from activated phagocytes and display intra- and extracellular functions. Their expression is ubiquitously observed in the squamous epithelia under normal, inflammatory and cancerous conditions. Immunohistochemical investigations have shown that the S100 proteins are over expressed in skin cancers, pulmonary adenocarcinoma, pancreatic adenocarcinoma, bladder cancers, ductal carcinoma of the breast, and prostate adenocarcinoma. In contrast, S100A8 and S100A9 are down-regulated in esophageal squamous cell carcinomas. Furthermore, plasma levels of S100A8/A9 are elevated in patients suffering from various cancers. Insofar, S100A8 and S100A9 might represent novel diagnostic markers for some carcinomas. S100A8 and S100A9 have been suggested to have potential roles in carcinogenesis and tumor progression. However, the biological role of S100A8/A9 remains to be elucidated. It is conceivable that S100A8 and S100A9 modulate signal pathways to directly promote invasion, migration and metastasis, probably via activation of NF-kB, Akt or MAP kinases. In the last decade the concept of the functional relationship between inflammation and cancer has been developed that is based on numerous findings, ranging from epidemiological studies to molecular analyses of mouse models (Coussens and Werb, 2002). In this concept, the generation of an inflammatory microenvironment supports tumorigenesis by promoting cancer cell survival, proliferation, migration, and invasion. Although it is clear that inflammation alone does not cause cancer, it is evident that an environment that is rich in inflammatory cells, growth factors, activated stroma, and DNA-damage-promoting agents certainly potentiates and/or promotes neoplastic risk. In addition, many cancers arise from sites of infection, chronic irritation and inflammation. Recent data have expanded our knowledge demonstrating that specific soluble factors released from primary tumors induce the S100A8 and S100A9 gene expression in the target tissue. After secretion S100A8 and S100A9 might display chemokine- and cytokine-like properties that promote invasion, migration and metastasis. These data indicate that tumor cells are able to reprogram some of the signaling molecules of the innate immune system. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development. |
Entity | Skin cancer |
Note | The expression of S100A8 and S100A9 in epithelial cells was first detected in the squamous epithelia (Gabrielsen et al., 1986). Normal S100A8 and S100A9 are expressed at minimal levels in the epidermis. However, their expression is induced in inflammatory and cancerous conditions, and pro-inflammatory cytokines such as TNF-alpha and IL1 beta are involved herein. Gene expression analysis in a mouse model of chemically induced skin carcinogenesis identified a large set of novel tumor-associated genes including S100A8 (Hummerich et al., 2006). The data was confirmed by in situ hybridization and immunofluorescence analysis on mouse tumor sections, in mouse keratinocyte cell lines that form tumors in vivo, and in human skin tumor specimens. However, conflicting results have been published concerning S100 expression in skin cancer. For instance, esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide. DNA microarray data analysis revealed that S100A8 and S100A9 were significantly down regulated in human ESCC versus the normal counterparts (Zhi et al., 2003). Interestingly, among the 42 genes either up regulated or down regulated in tumors, as compared to normal esophageal squamous epithelia, nine of the altered expression genes were related to arachidonic acid (AA) metabolism, suggesting that AA metabolism pathway and its altered expression may contribute to esophageal squamous cell carcinogenesis. Similar data were obtained by Ji et al. (2004). They investigated the differential expression of the S100 gene family at the RNA level in human ESCC. Eleven out of 16 S100 genes were significantly down regulated in ESCC versus the normal counterparts. Only the S100A7 gene was found to be markedly up regulated. Another study demonstrated that poorly differentiated ESCC displayed a stronger decrease in S100A8 and S100A9 expression than well and moderately differentiated tumors, with a correlation between protein level and histopathological grading (Kong et al., 2004). These findings suggest that decreased expression of S100A8 and S100A9 might play an important role in the ESCC pathogenesis, being particularly associated with poor differentiation of tumor cells. |
Entity | Lung adenocarcinomas |
Note | S100A9 over expression has been detected in various carcinomas of glandular cell origin, and its expression has been associated with poor tumor differentiation. Similarly, S100A9 immunopositivity was also detected in pulmonary adenocarcinoma cell lines and resected pulmonary adenocarcinoma (Arai et al., 2001). Examination of the relation of S100A9 expression to tumor differentiation showed that the expression rate in pulmonary adenocarcinoma showed higher correlation in poorly differentiated carcinomas. Another study confirmed these data (Su et al., 2010). Immunohistochemical staining of both S100 proteins showed a significant up-regulation in lung cancer tissue, and quantitative PCR revealed significantly higher levels of S100A8 and S100A9 mRNA transcripts in lung cancer tissues. Moreover, this study correlates S100A9 expression with inflammation and other clinical features (Su et al., 2010). Primary tumors influence the environment in the lungs before metastasis. They release specific soluble factors that prepare the premetastatic niche for the engraftment of tumor cells. In several studies it has been shown that tumor cells induce both expression and secretion of S100A8 and S100A9 in the target organ that display a promoting role in cancer cell survival, proliferation, migration, and invasion (Hiratsuka et al., 2002; Hiratsuka et al., 2006; Hiratsuka et al., 2008; Saha et al., 2010). Microarray analysis of lungs from tumor-bearing and non-bearing mice revealed the strong up-regulation of a number of genes including S100A8 and S100A9 (Hiratsuka et al. 2002). Their expression in Mac 1+-myeloid cells and endothelial cells was induced by factors such as vascular endothelial growth factor A (VEGF-A), tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta), both in vitro and in vivo (Hiratsuka et al., 2006). Remarkably, anti-S100A8 neutralizing antibody treatment blocked metastasis. S100A8 and S100A9 were shown to induce the expression of serum amyloid A (SAA) that attracted Mac 1+-myeloid cells in the premetastatic lung (Hiratsuka et al., 2008). These studies demonstrated that lung cancer cells utilize S100A8 and S100A9 as guidance for the adhesion and invasion of disseminating malignant cells. |
Entity | Pancreatic adenocarcinoma |
Note | Patients with ductal adenocarcinoma of the pancreas have a dismal prognosis. Thus, there is an urgent need for early detection markers and the development of immunotherapeutical approaches concentrating on the induction and enhancement of immune responses against tumors. Proteomic analyses of pancreatic adenocarcinoma, normal adjacent tissues, pancreatitis, and normal pancreatic tissues revealed a number of differentially expressed genes (Shen et al., 2004). S100A8 was found to be specifically over expressed in tumors compared with normal and pancreatitis tissues. These data are in accordance with another study (Sheikh et al., 2007). Strong expression of S100A8 and S100A9 was found in tumor-associated stroma but not in benign or malignant epithelia. Further analyses identified stromal CD14+ CD68- monocytes/macrophages as source for S100 expression. Interestingly, the number of S100A8-positive cells in the tumor microenvironment negatively correlated with the expression of the tumor suppressor protein, Smad4. The number of S100A9-positive cells was not altered in Smad4-negative or Smad4-positive tumors. A similar correlation was found in colorectal cancer tumors (Ang et al., 2010). The number of stromal S100A8- and S100A9-positive cells was associated with the presence or absence of Smad4. Smad4-negative tumors showed enhanced numbers of S100A8/A9 stroma cells, and the corresponding patients had a poor survival prognosis. Investigation of the underlying molecular mechanisms revealed that both migration and proliferation was enhanced in response to exogenous S100A8 and S100A9, irrespective of Smad4-presence. However, depletion of Smad4 resulted in loss of responsiveness to exogenous S100A8, but not S100A9. Vice versa, Smad4 expression in Smad4-negative cells enhanced the responsive-ness to S100A8 and S100A9. Further analyses give evidence that similar to TGF-beta, S100A8 and S100A9 induce the phosphorylation of both Smad2 and Smad3 that was blocked by a RAGE-specific antibody. These data point to a functional relationship between inflammation and tumorigenesis. |
Entity | Bladder cancers |
Note | Gene expression profiles revealed that thirteen members of the S100 gene family were differentially expressed in human bladder cancers. S100A8 and S100A9 were found to be over expressed (Yao et al., 2007). Another study investigated S100A9 expression and DNA methylation in urothelial cancer cell lines and cancer tissue (Dokun et al., 2008). Expression of S100A9 was found to be generally elevated in the tumor tissues but S100A9 was weakly expressed in most cancer cell lines. The S100A9 promoter contains 6 CpG sites, and its methylation state was unrelated to the variable expression. It has been hypothesized that over expression of genes is the consequence of DNA hypomethylation, however, DNA methylation and gene expression are less strictly related for those genes having promoters within CpG-islands. Alternatively, the increased S100A9 gene expression may be related to that of other immune-related genes in the carcinoma cell cultures. This is sustained by the facts that S100A9 is secreted by epithelial and other cell types to modulate inflammatory reactions as well as to promote cancer proliferation and metastasis. Two recent studies propose S100A8 and S100A9 gene expression as prognostic value for bladder cancer (Minami et al., 2010; Ha et al., 2010). By proteomic analysis of pre- and postoperative sera from bladder cancer patients S100A8 and S100A9 were identified as tumor-associated proteins (Minami et al., 2010). Interestingly, S100A8 expression was associated with bladder wall muscle invasion of the tumor and cancer-specific survival while S100A9 expression was associated with the tumor grade. In addition, the expression of both proteins S100A8/A9 was correlated with recurrence-free survival. In another study it was evaluated whether S100A8 is a prognostic value for non-muscle-invasive bladder cancer (NMIBC) (Ha et al., 2010). S100A8 expression was evaluated in a total of 103 primary NMIBC samples by quantitative PCR. The mRNA expression levels of S100A8 were significantly related to the progression of NMIBC, suggesting that S100A8 might be a useful prognostic marker for disease progression of NMIBC. |
Entity | Breast cancers |
Note | S100A8 and S100A9 are expressed in breast cancers (Cross et al., 2005), especially in invasive breast carcinoma (Arai et al., 2004). By immunohistochemical analyses a strong S100A9 immunoreactivity has been demonstrated in invasive as well as non-invasive ductal carcinoma. No immunopositive reaction was observed in invasive lobular carcinomas, and no significant differences were detected in the number of myelomonocytic cells expressing S100A9. These data give evidence that S100A9 in glandular epithelial cells is newly expressed under cancerous conditions and is over-expressed in poorly differentiated adenocarcinoma (Arai et al., 2004). Further analyses target on the relationship between S100A8/A9 expression and pathological parameters that reflect the aggressiveness of carcinoma. The immunopositivity for S100A8/A9 correlated with poor tumor differentiation, mitotic activity, HER2/neu over expression, poor pT categories, node metastasis, and poor pStage, but not with vessel invasion. These data may indicate that S100A8 and S100A9 over expression should be considered marker of poor prognosis in invasive breast ductal carcinoma (Arai et al., 2008). By analyses of ductal carcinoma in situ and invasive ductal carcinoma of the breast S100A9 has been demonstrated to be most abundantly expressed in the invasive tumor (Seth et al., 2003). Therefore, the expression of S100A8 and S100A9 has been correlated with the degree of noninvasive / invasive behavior. There are conflicting data concerning this correlation. For instance, non-invasive MCF-7 breast cancer cells do not express S100A9, and its gene expression is induced by cytokine oncostatin M through the STAT3 signaling cascade (Li et al., 2004). However, non-invasive MDA-MB-468 cells are abundant for both S100 proteins (Bode et al., 2008) and invasive breast cancer cells MDA-MB-231 show low transcript level of S100A9 (Nagaraja et al., 2006). |
Entity | Thyroid carcinoma |
Note | Similar to other carcinomas of glandular cell origin, expression of S100A8 and S100A9 is significantly linked to dedifferentiation of thyroid carcinoma (Ito et al., 2005; Ito et al., 2009). S100A8 and S100A9 immunreactivity was found in all undifferentiated carcinomas examined, while papillary carcinoma, follicular carcinoma, follicular adenoma and medullary carcinoma and normal follicules were negative for both proteins. Further analyses revealed that S100A9 is a useful marker for discriminating intrathyroid epithelial tumor from squamous cell carcinoma or undifferentiated carcinoma with squamoid component (Ito et al., 2006). |
Entity | Prostate cancer |
Note | Increased levels of S100A8, S100A9, and RAGE have been reported in prostatic intra epithelial neoplasia and preferentially in high-grade adenocarcinomas, whereas benign tissue was negative or showed weak expression of the proteins. The three proteins showed a strong overlap in the expression pattern. S100A9 serum level was significantly elevated in cancer patients compared with benign prostatic hyperplasia patients or healthy individuals. Therefore, S100A8 and S100A9 might represent novel diagnostic markers for prostate cancer and benign prostate hyperplasia (Hermani et al., 2005). In further analyses it has been demonstrated that S100A8 and S100A9 are secreted by prostate cancer cells, and extracellular S100A8/A9 stimulates migration of benign prostatic cells in vitro by activation of NF-kB and increased phosphorylation of p38 and p44/p42 MAP kinases. Immunofluorescence analyses give evidence for a RAGE-mediated response (Hermani et al., 2006). The significance of being diagnostic markers for prostate cancer has been questioned by Ludwig et al. (2007). Their re-evaluation study has shown that S100A8/A9 did not improve the differentiation between patients with and without prostate cancer. The data give no evidence for the replacement of the established marker PSA by S100A8/A9. |
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Citation |
This paper should be referenced as such : |
Kerkhoff, C ; Ghavami, S |
S100A9 (S100 calcium binding protein A9) |
Atlas Genet Cytogenet Oncol Haematol. 2011;15(9):746-757. |
Free journal version : [ pdf ] [ DOI ] |
Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ] |
t(1;19)(q21;p13) R3HDM4/S100A9
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