Decorin-Mediated Effects in Cancer Cell Biology

Zafiropoulos, Alexandros; Tzanakakis, George N.

doi:10.1080/03008200802147746

Cited by 15 publications

(12 citation statements)

References 35 publications

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“…Decorin is a key modulator of the tumour microenvironment [27] through interactions with EGFR and MAPK [28] pathways. Decorin also activates insulin-like growth factor-I receptor [29], attenuates Erb2 signalling [30], binds to TGF-Beta, activates Met and up-regulates p21 [31] [32]. While in most studies DCN has been found to have an antioncogenic role, others correlate DCN with increased migration of human osteosarcoma cells [33] and high expression in endothelial cells undergoing angiogenesis [34].…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analyses Reveal High Expression of Decorin and Endoplasmin (HSP90B1) Are Associated with Breast Cancer Metastasis and Decreased Survival

Cawthorn

Moreno

Dharsee³

et al. 2012

PLoS ONE

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BackgroundBreast cancer is the most common malignancy among women worldwide in terms of incidence and mortality. About 10% of North American women will be diagnosed with breast cancer during their lifetime and 20% of those will die of the disease. Breast cancer is a heterogeneous disease and biomarkers able to correctly classify patients into prognostic groups are needed to better tailor treatment options and improve outcomes. One powerful method used for biomarker discovery is sample screening with mass spectrometry, as it allows direct comparison of protein expression between normal and pathological states. The purpose of this study was to use a systematic and objective method to identify biomarkers with possible prognostic value in breast cancer patients, particularly in identifying cases most likely to have lymph node metastasis and to validate their prognostic ability using breast cancer tissue microarrays.Methods and FindingsDifferential proteomic analyses were employed to identify candidate biomarkers in primary breast cancer patients. These analyses identified decorin (DCN) and endoplasmin (HSP90B1) which play important roles regulating the tumour microenvironment and in pathways related to tumorigenesis. This study indicates that high expression of Decorin is associated with lymph node metastasis (p<0.001), higher number of positive lymph nodes (p<0.0001) and worse overall survival (p = 0.01). High expression of HSP90B1 is associated with distant metastasis (p<0.0001) and decreased overall survival (p<0.0001) these patients also appear to benefit significantly from hormonal treatment.ConclusionsUsing quantitative proteomic profiling of primary breast cancers, two new promising prognostic and predictive markers were found to identify patients with worse survival. In addition HSP90B1 appears to identify a group of patients with distant metastasis with otherwise good prognostic features.

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Section: Discussionmentioning

confidence: 99%

Proteomic Analyses Reveal High Expression of Decorin and Endoplasmin (HSP90B1) Are Associated with Breast Cancer Metastasis and Decreased Survival

Cawthorn

Moreno

Dharsee³

et al. 2012

PLoS ONE

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“…Previous evidence suggests that decorin, as a key component of the tumor stroma, interacts with various growth factors such as EGF and TGF-β and is necessary for cell migration (34,35). Furthermore, it may regulate the action of several tyrosine-kinase receptors, including the EGFR, ERK and insulin-like growth factor receptor I (36,37).…”

Section: Discussionmentioning

confidence: 99%

Asporin participates in gastric cancer cell growth and migration by influencing EGF receptor signaling

2015

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Abstract. Asporin (ASPN), a novel member of the small leucine-rich proteoglycan (SLRP) family, serves as a key component of the tumor stroma and has been reported to be abnormally expressed in certain types of tumors. Specifically, the proteoglycan was proven to activate the coordinated invasion of scirrhous gastric cancer and cancer-associated fibroblasts. However, the role of ASPN in cancer cell growth and metastasis has not yet been addressed. In the present study, we aimed to evaluate the tumoricidal benefits of ASPN on tumorigenesis and progression of gastric cancer. Firstly, it was demonstrated that ASPN was overexpressed in gastric carcinoma tissues when compared to the corresponding non-cancerous tissues, and it had varied levels of expression in gastric cancer epithelial cell lines. Additionally, we assessed the effects of transient siRNA-mediated ASPN knockdown on gastric cancer cells. ASPN silencing inhibited proliferation and suppressed the migration of immortalized neoplastic epithelial cells. Furthermore, at the molecular level, we found that downregulation of ASPN blocked the anti-apoptotic molecule Bcl-2, increased the expression of pro-apoptotic molecule Bad, reduced the expression of migration-related proteins CD44 and matrix metalloproteinase (MMP)-2, and abrogated the activation of the phosphorylation status of ERK and epidermal growth factor (EGF) and its receptor (EGFR). Collectively, our findings indicate that ASPN is upregulated and plays an oncogenic role in gastric cancer progression and metastasis by influencing the EGFR signaling pathway.

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“…However, studies by us and others have shown that decorin is expressed by oral squamous cell carcinoma and osteosarcoma cells [20,21]. Osteosarcoma cells were shown to be insensitive to decorin-induced growth arrest, rather decorin seemed to be beneficial, since it was necessary for osteosarcoma cell migration [22]. …”

Section: Introductionmentioning

confidence: 99%

A role for aberrantly expressed nuclear localized decorin in migration and invasion of dysplastic and malignant oral epithelial cells

Dil

Banerjee

2011

Head Neck Oncol

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BackgroundOral cancer is the sixth most common malignancy worldwide with a mortality rate that is higher than many other cancers. Death usually occurs as a result of local invasion and regional lymph node metastases. Decorin is a multifunctional proteoglycan of the extracellular matrix that affects the biology of various types of cancer. Previously; we have shown that decorin is aberrantly expressed in the nucleus in human dysplastic oral keratinocytes (DOK) and malignant squamous cells carcinoma (SCC-25) and human biopsy tissues. In this study, we examined the role of nuclear decorin in oral cancer progression.Materials and methodsWe have used a post-transcriptional gene silencing (RNA interference) approach to stably knockdown nuclear decorin gene expression in DOK and SCC-25 cells using a specific shRNA plasmid and a combination of immunological and molecular techniques to study nuclear decorin function in these oral epithelial cell lines.ResultsMore than 80% decorin silencing/knockdown was achieved as confirmed by real time PCR and western blot analysis in both DOK and SCC-25 cells. This RNA interference-mediated knockdown of nuclear decorin expression resulted in significantly reduced invasion and migration in these cell lines as measured by Matrigel™ coated and uncoated Trans well chamber assays respectively. Decorin silencing also resulted in reduced IL-8 mRNA and proteins levels in these cell lines. Culturing decorin silenced DOK and SCC-25 cells, with recombinant human IL-8 or IL-8 containing conditioned medium from respective un-transfected cells for 24 h prior to migration and invasion experiments, resulted in the salvation of reduced migration and invasion phenotype. Furthermore, we found that nuclear localized decorin interacts with EGFR in the nuclear fractions of both DOK and SCC-25 cells. Interestingly, EGFR (trans) activation has previously been shown to be involved in IL-8 production in various epithelia.ConclusionsTaken together, our results indicate that nuclear localized decorin plays an important role in migration and invasion of oral cancer cells and thus may present as a novel potential target for the treatment of oral cancer.

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Decorin-Mediated Effects in Cancer Cell Biology

Cited by 15 publications

References 35 publications

Proteomic Analyses Reveal High Expression of Decorin and Endoplasmin (HSP90B1) Are Associated with Breast Cancer Metastasis and Decreased Survival

Proteomic Analyses Reveal High Expression of Decorin and Endoplasmin (HSP90B1) Are Associated with Breast Cancer Metastasis and Decreased Survival

Asporin participates in gastric cancer cell growth and migration by influencing EGF receptor signaling

A role for aberrantly expressed nuclear localized decorin in migration and invasion of dysplastic and malignant oral epithelial cells

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