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Differential role of psoriasin (S100A7) in estrogen receptor ? positive and negative breast cancer cells occur through actin remodeling.

ABSTRACT: Psoriasin (S100A7) is a calcium-binding protein that has shown to be highly expressed in high-grade ductal carcinoma in situ (DCIS) and a subset of invasive breast cancers. However, its role in invasion and metastasis is not very well known. In this study, we have shown that S100A7 differentially regulates epidermal growth factor (EGF)-induced cell migration and invasion in ER?(-) MDA-MB-231 cells and ER?(+) MCF-7 and T47D breast cancer cells. Further signaling studies revealed that S100A7 enhances EGF-induced EGFR phosphorylation and actin remodeling that seems to favor lamellipodia formation in ER?(-) cells. In addition, S100A7 overexpression enhanced NF-?B-mediated matrix metalloproteinase-9 (MMP-9) secretion in MDA-MB-231 cells indicating its role in enhanced invasiveness. However, S100A7 overexpression inhibited migration and invasion of MCF-7 cells by inactivating Rac-1 pathway and MMP-9 secretion. Moreover, S100A7 overexpressing MDA-MB-231 cells showed enhanced metastasis compared to vector control in in vivo nude mice as detected by bioluminescence imaging. Our tissue microarray data also revealed predominant expression of S100A7 in ER?(-) metastatic carcinoma, especially in lymph node regions. Overall these studies suggest that S100A7 may enhance metastasis in ER?(-) breast cancer cells by a novel mechanism through regulation of actin cytoskeleton and MMP-9 secretion.

SUBMITTER: Sneh A

PROVIDER: S-EPMC4070432 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Differential role of psoriasin (S100A7) in estrogen receptor α positive and negative breast cancer cells occur through actin remodeling.

Sneh Amita A Deol Yadwinder S YS Ganju Akaansha A Shilo Konstantin K Rosol Thomas J TJ Nasser Mohd W MW Ganju Ramesh K RK

Breast cancer research and treatment 20130328 3

Psoriasin (S100A7) is a calcium-binding protein that has shown to be highly expressed in high-grade ductal carcinoma in situ (DCIS) and a subset of invasive breast cancers. However, its role in invasion and metastasis is not very well known. In this study, we have shown that S100A7 differentially regulates epidermal growth factor (EGF)-induced cell migration and invasion in ERα(-) MDA-MB-231 cells and ERα(+) MCF-7 and T47D breast cancer cells. Further signaling studies revealed that S100A7 enhan ...[more]

PMID: 23535840

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Project description:Identification of the proteins that are associated with estrogen receptor (ER) status is a first step towards better understanding of the hormone-dependent nature of breast carcinogenesis. Although a number of gene expression analyses have been conducted, protein complement has not been systematically investigated to date. Because proteins are primary targets of therapeutic drugs, in this study, we have attempted to identify proteomic signatures that demarcate ER-positive and -negative breast cancers. Using highly enriched breast tumor cells, replicate analyses from 3 ERα+ and 3 ERα- human breast tumors resulted in the identification of 2,995 unique proteins with ≥2 peptides. Among these, a number of receptor tyrosine kinases and intracellular kinases that are abundantly expressed in ERα+ and ERα- breast cancer tissues were identified. Further, label-free quantitative proteome analysis revealed that 236 proteins were differentially expressed in ERα+ and ERα- breast tumors. Among these, 141 proteins were selectively up-regulated in ERα+, and 95 proteins were selectively up-regulated in ERα- breast tumors. Comparison of differentially expressed proteins with a breast cancer database revealed 98 among these have been previously reported to be involved in breast cancer. By Gene Ontology molecular function, dehydrogenase, reductase, cytoskeletal proteins, extracellular matrix, hydrolase, and lyase categories were significantly enriched in ERα+, whereas selected calcium-binding protein, membrane traffic protein, and cytoskeletal protein were enriched in ERα- breast tumors. Biological process and pathway analysis revealed that up-regulated proteins of ERα+ were overrepresented by proteins involved in amino acid metabolism, proteasome, and fatty acid metabolism, while up-regulated proteins of ERα- were overrepresented by proteins involved in glycolysis pathway. The presence and relative abundance of 4 selected differentially abundant proteins (liprin-α1, fascin, DAP5, and β-arrestin-1) were quantified and validated by immunohistochemistry. In conclusion, unlike in vitro cell culture models, the in vivo signaling proteins and pathways that we have identified directly from human breast cancer tissues may serve as relevant therapeutic targets for the pharmacological intervention of breast cancer.

Project description:BACKGROUND: Progressive airway inflammation and susceptibility to the airway colonisation and infection are characteristic for the pathophysiology of chronic obstructive pulmonary disease (COPD). Antimicrobial peptides (AMPs) are central to the function of the innate host immune response against microbial pathogens and are regulators of inflammation and immunity. S100A7/psoriasin, a recently described AMP, is an essential component of the human epithelia against invading pathogens and acts as an effector molecule of the host innate defence in the skin. We hypothesized that S100A7/psoriasin is involved in the airway mucosal immunity and differently regulated and expressed in the lung during progression of COPD. METHODS: S100A7/psoriasin gene expression was assessed in bronchial biopsies and bronchoalveolar lavage (BAL) fluid cells of healthy controls and COPD patients. Using confocal microscopy and immunohistochemistry, the protein expression of S100A7/psoriasin was investigated. RESULTS: Here, we report that S100A7/psoriasin, the major antimicrobial peptide of the human skin, is constitutively expressed in perinuclear granules of human bronchial epithelial cells and alveolar macrophages. Whereas typical activators of the innate immune response like TLR ligands and cytokines induced the upregulation of CXCL-8 mRNA and release of CXCL-8 by epithelial cells, S100A7/psoriasin mRNA expression was not modulated. To investigate a potential association of S100A7/psoriasin with COPD, S100A7/psoriasin mRNA expression was assessed in bronchial biopsies and BAL fluid cells of patients at different stages of COPD and controls. Overall, 10 healthy individuals and 34 COPD patients were enrolled in this study. We found an association of S100A7/psoriasin mRNA expression with bacterial detection in the tracheobronchial system (p = 0.0304), which was the strongest in individuals positive for with S. aureus (p = 0.0005). However, S100A7/psoriasin mRNA expression was not altered during the progression of COPD. CONCLUSIONS: S100A7/psoriasin gene expression is unchanged in the airways during COPD. The newly identified association of S100A7/psoriasin with S. aureus may provide new insights into the antimicrobial defence response of the human airways, leading to the induction of S100A7/psoriasin upon microbial challenge.

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Differential role of psoriasin (S100A7) in estrogen receptor ? positive and negative breast cancer cells occur through actin remodeling.

Publications

Differential role of psoriasin (S100A7) in estrogen receptor α positive and negative breast cancer cells occur through actin remodeling.

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