Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Dermatan sulfate is involved in the tumorigenic properties of Esophagus Squamous Cell Carcinoma

ABSTRACT: Extracellular matrix, either produced by cancer cells or by cancer-associated fibroblasts, influences angiogenesis, invasion and metastasis. Chondroitin/dermatan sulfate (CS/DS) proteoglycans, which occur both in the matrix and at the cell surface, play important roles in these processes. The unique feature that distinguishes DS from CS is the presence of iduronic acid (IdoA) in DS. The main IdoA-producing enzyme, DS epimerase 1 (DS-epi1) was highly up-regulated in ESCC biopsies. To further understand the roles of IdoA in tumor development, DS-epi1 expression, and consequently IdoA content, was downregulated in ESCC cells. IdoA-deficient cells exhibited decreased migration and invasion capabilities in vitro, which was associated with reduced cellular binding of hepatocyte growth factor, inhibition of pERK-1/2 signaling, and de-regulated actin cytoskeleton dynamics and focal adhesion formation. Our findings demonstrate that IdoA in DS influences tumorigenesis by affecting cancer cell behavior. Gene expression data including 10 Esophageal squamous carcinoma specimens and 27 gastroesophageal adenocarcinoma specimens.

ORGANISM(S): Homo sapiens

SUBMITTER: Anna Ekstrand

PROVIDER: E-GEOD-27040 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Dermatan sulfate is involved in the tumorigenic properties of esophagus squamous cell carcinoma.

Thelin Martin A MA Thelin Martin A MA Svensson Katrin J KJ Shi Xiaofeng X Bagher Mariam M Axelsson Jakob J Isinger-Ekstrand Anna A van Kuppevelt Toin H TH Johansson Jan J Nilbert Mef M Zaia Joseph J Belting Mattias M Maccarana Marco M Malmström Anders A

Cancer research 20120220 8

Extracellular matrix, either produced by cancer cells or by cancer-associated fibroblasts, influences angiogenesis, invasion, and metastasis. Chondroitin/dermatan sulfate (CS/DS) proteoglycans, which occur both in the matrix and at the cell surface, play important roles in these processes. The unique feature that distinguishes DS from CS is the presence of iduronic acid (IdoA) in DS. Here, we report that CS/DS is increased five-fold in human biopsies of esophagus squamous cell carcinoma (ESCC), ...[more]

PMID: 22350411

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Project description:Background: The amplification event occurring at chromosome locus 11q13, reported in several different cancers, includes a number of potential oncogenes. We have previously reported amplification of one such oncogene, CCND1, to be correlated with an adverse effect of tamoxifen in premenopausal breast cancer patients. Overexpression of cyclin D1 protein however, confers tamoxifen resistance but not a tamoxifen induced adverse effect. Potentially, co-amplification of an additional 11q13 gene, with a resulting protein overexpression, is required to cause an agonistic effect. Moreover, during 11q13 amplification a deletion of the distal 11q region has been described. In order to assess the potential impact of the deletion we have examined a selected marker for this event. Methods: Array CGH analysis was employed to identify and confirm changes in the gene expression of a number of different genes mapping to the 11q chromosomal region, associated with CCND1 amplification. The subsequent protein expression of these candidate genes was then examined in a clinical material of 500 primary breast cancers from premenopausal patients randomized to either tamoxifen or no adjuvant treatment. The protein expression was also compared to the CGH data in a subset of 56 breast cancer samples. Results: Cortactin and FADD overexpression was linked to CCND1 amplification, determined by FISH, but was not associated with a diminished effect of tamoxifen. However, deletion of distal chromosome 11q, defined as downregulation of the marker Chk1, was associated with an impaired tamoxifen response, and interestingly, also with low proliferative breast cancer of low grade. For Pak1 and cyclin D1 the protein expression corresponded to the gene expression data from the CGH analysis. Conclusions: The results indicate that many 11q13 associated gene products are overexpressed in conjunction with cyclin D1 but not linked to an agonistic effect of tamoxifen. Finally, the deletion of distal 11q, linked to 11q13 amplification, might be an important event affecting breast cancer outcome and tamoxifen response. Keywords: comparative genomic hybridisation 56 samples with 11q13 amplification have been analysed and compared with protein expression results from immunohistochemical analyses.

Dataset Information

Dermatan sulfate is involved in the tumorigenic properties of Esophagus Squamous Cell Carcinoma

Publications

Dermatan sulfate is involved in the tumorigenic properties of esophagus squamous cell carcinoma.

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