S100A8/A9: A Janus-faced molecule in cancer therapy and tumorgenesis

Ghavami, Saeid; Chitayat, Seth; Hashemi, Mohammad; Eshraghi, Mehdi; Chazin, Walter J.; Halayko, Andrew J.; Kerkhoff, Claus

doi:10.1016/j.ejphar.2009.08.044

Cited by 102 publications

(114 citation statements)

References 140 publications

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“…S100A8/A9 has also been reported to mediate NF-κB for tumorigenesis (Ghavami et al, 2009;Hermani et al, 2006). Therefore, NF-κB activity was determined by a luciferase reporter assay using an NF-κB reporter construct.…”

Section: Resultsmentioning

confidence: 99%

S100A8 and S100A9 Promotes Invasion and Migration through p38 Mitogen-Activated Protein Kinase-Dependent NF-κB Activation in Gastric Cancer Cells

Kwon

Moon

Park

et al. 2013

Molecules and Cells

105

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S100A8 and S100A9 (S100A8/A9) are low-molecular weight members of the S100 family of calcium-binding proteins. Recent studies have reported S100A8/A9 promote tumorigenesis. We have previously reported that S100A8/A9 is mostly expressed in stromal cells and inflammatory cells between gastric tumor cells. However, the role of environmental S100A8/A9 in gastric cancer has not been defined. We observed in the present study the effect of S100A8/A9 on migration and invasion of gastric cancer cells. S100A8/ A9 treatment increased migration and invasionat lower concentrations that did not affect cell proliferation and cell viability. S100A8/A9 caused activation of p38 mitogenactivated protein kinase (MAPK) and nuclear factor-κB (NF-κB). The phosphorylation of p38 MAPK was not affected by the NF-κB inhibitor Bay whereas activation of NF-κB was blocked by p38 MAPK inhibitor SB203580, indicating that S100A8/A9-induced NF-κB activation is mediated by phosphorylation of p38 MAPK. S100A8/A9-induced cell migration and invasion was inhibited by SB203580 and Bay, suggesting that activation of p38 MAPK and NF-κB is involved in the S100A8/A9 induced cell migration and invasion. S100A8/A9 caused an increase in matrix metalloproteinase 2 (MMP2) and MMP12 expression, which were inhibited by SB203580 and Bay. S100A8/A9-induced cell migration and invasion was inhibited by MMP2 siRNA and MMP12 siRNA, indicating that MMP2 and MMP12 is related to the S100A8/A9 induced cell migration and invasion. Taken together, these results suggest that S100A8/A9 promotes cell migration and invasion through p38 MAPKdependent NF-κB activation leading to an increase of MMP2 and MMP12 in gastric cancer.

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Section: Resultsmentioning

confidence: 99%

S100A8 and S100A9 Promotes Invasion and Migration through p38 Mitogen-Activated Protein Kinase-Dependent NF-κB Activation in Gastric Cancer Cells

Kwon

Moon

Park

et al. 2013

Molecules and Cells

105

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“…Bone marrow (BM)-derived HPCs expressing VEGFR1 were shown to precede arrival of DTCs at distant sites in the lungs. S100A8 and S100A9 acting as inflammatory chemoattractants and inducers of inflammatory pathways were identified as key molecules for implementation of metastatic niches (55,56). They act as inducers of serum amyloid A3 (SAA3) which mediates accumulation of CD11 + myeloid cells via interaction with TLR4 and stimulation of NF-ĸB signaling (57).…”

Section: Concept Of Pre-and Metastatic Nichementioning

confidence: 99%

The Multiple Roles of Exosomes in Metastasis

Weidle

Birzele

Kollmorgen

et al. 2017

CGP

164

133

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Abstract. Exosomes are important contributors to cellMetastases are responsible for the death of a large majority of cancer patients despite considerable progress in surgical techniques, radiotherapy, chemotherapy and targeted therapies including immuno-therapy (1). A dramatic reduction of metastatic burden has been observed, however, tumor elimination is almost always incomplete. This phenomenon is based on drug resistance, which is due to adaptation of intracellular pathways or on activation of survival-supporting autocrine and paracrine pathways and several secreted factors expressed by drug-sensitive tumor cells after therapy (2). Metastasis can occur through release of cancer cells from the primary tumor into body cavities that holds true for ovarian and CNS tumors, or via hematogeneous and lymphatic vessels of the circulatory system (3). Metastases of some tumors are directed besides to lymph nodes to mainly one type of organ only, such as prostate cancer to the bones, pancreatic cancer and uveal melanoma to the liver, whereas tumors such as melanoma, breast-and lung cancer can colonize several types of organs (3). Tumor cells have been found in the blood of patients with early-stage cancer and in some cases even before the primary tumor has been diagnosed (4, 5). Recently, making use of single-cell expression profiling, it has been shown that early metastatic cells possess a stem-like gene signature and give rise to heterogeneous metastases (6). The metastatic process is characterized by a defined sequence of events (7,8). Initial steps are detachment from the extracellular matrix (ECM), invasion into the surrounding tissue and proteolysis of the basement membrane. After intravasation, survival of circulating tumor cells (CTCs) is achieved by forming clusters, binding to platelets and immune evasion. Subsequently, they arrest in distal microvascular beds and extravasation can be achieved either by migration through intercellular junctions of endothelial cells (EC) or penetration of a single EC (9). CTCs can also colonize their tumors of origin, a process referred to as "tumor self-seeding", selecting for cancer cell populations more aggressive than those present in the primary tumor (10). After extravasation, colonization and outgrowth in the parenchyma of distant organs are the following steps. A common theme of the metastatic process is settlement of disseminated tumor cells (DTCs) into latency (dormancy), which can last from several months to decades (11). It has been observed that DTCs are recruited into pre-metastatic niches that support their survival by interactions with endothelial, myeloid cells, fibroblasts and other types of cells. After adaptation to the host microenvironment and suppression of an anti-tumoral immune response, DTCs are activated by not yet completely resolved mechanisms. Finally their outgrowth is based on an angiogenic switch mediated by pro-angiogenic factors and establishment of a vascular network to support the metabolic demands of colonizing tumor cells (12). In the follo...

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“…The overexpression of this acute phase protein in human lung cancer tissues has been confirmed by immunohistochemistry and Western blot (37). Notably, primary tumors of lung could release soluble factors that induce the expression human calprotectin, which could facilitate the survival and proliferation of metastasizing cancer cells (38). Human calprotectin is the complex of S100A8 and S100A9.…”

Section: Fig 5 Performance Of Biomarker Panelmentioning

confidence: 94%

Proteomic Analysis of Human Saliva From Lung Cancer Patients Using Two-Dimensional Difference Gel Electrophoresis and Mass Spectrometry

Xiao¹,

Zhang²,

Zhou³

et al. 2012

Molecular & Cellular Proteomics

161

108

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Lung cancer is often asymptomatic or causes only nonspecific symptoms in its early stages. Early detection represents one of the most promising approaches to reduce the growing lung cancer burden. Human saliva is an attractive diagnostic fluid because its collection is less invasive than that of tissue or blood. Profiling of proteins in saliva over the course of disease progression could reveal potential biomarkers indicative of oral or systematic diseases, which may be used extensively in future medical diagnostics. There were 72 subjects enrolled in this study for saliva sample collection according to the approved protocol. Two-dimensional difference gel electrophoresis combined with MS was the platform for salivary proteome separation, quantification, and identification from two pooled samples. Candidate proteomic biomarkers were verified and prevalidated by using immunoassay methods. There were 16 candidate protein biomarkers discovered by two-dimensional difference gel electrophoresis and MS. Three proteins were further verified in the discovery sample set, prevalidation sample set, and lung cancer cell lines. The discriminatory power of these candidate biomarkers in lung cancer patients and healthy control subjects can reach 88.5% sensitivity and 92.3% specificity with AUC ‫؍‬ 0.90. This preliminary data report demonstrates that proteomic biomarkers are present in human saliva when people develop lung cancer. The discriminatory power of these candidate biomarkers indicate that a simple saliva test might be established for lung cancer clinical screening and detection. Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.012112, 1-12, 2012.Lung cancer has long been a significant worldwide public health issue. In the United States, lung cancer is the most common cause of cancer-related death in men and women. According to the American Cancer Society, the major type of lung cancer is non-small-cell lung cancer (NSCLC) 1 , which comprises ϳ85% of lung cancers (1, 2). Small cell lung cancer (SCLC) is another type of lung cancer, which represents about 15% of cases (3). Cigarette smoking causes lung cancer, which is by far the major risk factor (4, 5, 6). Lung cancer has a high mortality rate among malignancies, in part because symptoms are frequently absent until disease is already metastatic and is, therefore, incurable (7,8,9). Early detection represents a very promising approach to reduce lung cancer incidence and mortality. However, conventional diagnostic methods for lung cancer are unsuitable for widespread screening because they are either expensive and occasionally miss tumors or invasive cancer (10,11,12,13). Computed tomography has been wildly used for lung cancer early screening, although it often produces a high rate of false positives (7,14,15). Better diagnostic methods are urgently needed to improve the detection of lung cancer.Tissue and blood have been extensively used in attempts to detect lung cancer earlier (1,16,17,18). Sputum has also been used to predict lung cancer by detecting its aberra...

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S100A8/A9: A Janus-faced molecule in cancer therapy and tumorgenesis

Cited by 102 publications

References 140 publications

S100A8 and S100A9 Promotes Invasion and Migration through p38 Mitogen-Activated Protein Kinase-Dependent NF-κB Activation in Gastric Cancer Cells

S100A8 and S100A9 Promotes Invasion and Migration through p38 Mitogen-Activated Protein Kinase-Dependent NF-κB Activation in Gastric Cancer Cells

The Multiple Roles of Exosomes in Metastasis

Proteomic Analysis of Human Saliva From Lung Cancer Patients Using Two-Dimensional Difference Gel Electrophoresis and Mass Spectrometry

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