Differentiation of Mesothelioma Cells Is Influenced by the Expression of Proteoglycans

Dobra, Katalin; Andäng, Michael; Syrokou, Alexandra; Karamanos, Nikos K.; Hjerpe, Anders

doi:10.1006/excr.2000.4915

Cited by 67 publications

(65 citation statements)

References 36 publications

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“…This is consistent with the predominant expression of decorin in mesenchymal cells (35,36). We also demonstrated that decorin and biglycan significantly diminished WISP-1 interaction.…”

Section: Wisp-1 Binds To Decorin At the Surface Of Human Skinsupporting

confidence: 90%

WISP-1 Binds to Decorin and Biglycan

Desnoyers¹,

Arnott²,

Pennica³

2001

Journal of Biological Chemistry

110

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Wnt-1-induced secreted protein 1 (WISP-1) is a member of the CCN (connective tissue growth factor, Cyr61, NOV) family of growth factors. Structural and experimental evidence suggests that CCN family member activities are modulated by their interaction with sulfated glycoconjugates. To elucidate the mechanism of action for WISP-1, we characterized the specificity of its tissue and cellular interaction and identified binding factors. WISP-1 binding was restricted to the stroma of colon tumors and to cells with a fibroblastic phenotype. By using a solid phase assay, we showed that human skin fibroblast conditioned media contained WISP-1 binding factors. Competitive inhibition with different glycosaminoglycans and treatment with glycosaminoglycan lyases and proteases demonstrated that binding to the conditioned media was mediated by dermatan sulfate proteoglycans. Mass spectrometric analysis identified the isolated binding factors as decorin and biglycan. Decorin and biglycan interacted directly with WISP-1 and inhibited its binding to components in the conditioned media. Similarly, WISP-1 interaction with human skin fibroblasts was inhibited by dermatan sulfate, decorin, and biglycan or by treatment of the cell surface with dermatan sulfate-specific lyases. Together these results demonstrate that decorin and biglycan are WISP-1 binding factors that can mediate and modulate its interaction with the surface of fibroblasts. We propose that this specific interaction plays a role in the regulation of WISP-1 function.

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“…This is consistent with the predominant expression of decorin in mesenchymal cells (35,36). We also demonstrated that decorin and biglycan significantly diminished WISP-1 interaction.…”

Section: Wisp-1 Binds To Decorin At the Surface Of Human Skinsupporting

confidence: 90%

WISP-1 Binds to Decorin and Biglycan

Desnoyers¹,

Arnott²,

Pennica³

2001

Journal of Biological Chemistry

110

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“…Resulting sequences were compared to the GenBank and EMBL databases using the BLAST program. Data from this study, Douglas and Quinlan (1991) and Fischer and Quinlan (1998a,b) dierentiated tumor cells have been reported to express higher levels of biglycan (Dobra et al, 2000). Nidogen/ entactin bridges the ECM molecules laminin 1 and type IV collagen.…”

Section: Extracellular Matrix and Adhesion Proteins And Proteoglycansmentioning

confidence: 50%

Identification of genes involved in epithelial-mesenchymal transition and tumor progression

2001

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The adenovirus E1A12S gene product (WT12S) immortalizes epithelial cells and they retain their dierentiated characteristics, but certain mutants cannot do the latter. Characterization of mutant immortalized epithelial cells indicated that they had undergone epithelial mesenchymal transition (EMT). Coexpression of V12ras with WT12S leads to benign tumors, but to malignant tumors with 12S mutants. Since EMT is critical for tumor progression, identi®cation of the molecular mechanisms involved should elucidate novel therapeutic targets. To this end, representational dierence analysis (RDA) was used to identify cDNAs upregulated in the mutant cell line. Thirty-®ve dierentially expressed mRNAs were identi®ed and classi®ed into several functional categories, including nine novel cDNAs. Among the 26 known cDNAs, extracellular matrix and related proteins made up the largest group of dierentially expressed genes, followed by growth factors and receptors and transcription factors. There was also an ion transporter, a cytoskeletal protein, glycosylation and amidinotransferase enzymes and proteins with unknown functions. Some of the known genes have previously been associated with EMT and/or tumor progression and thus served to validate the system to obtain the desired target genes, while other cDNAs are newly linked with dedierentiation/malignancy. Array analyses indicated that the cDNAs were speci®cally upregulated in invasive or metastatic tumors, especially of breast, uterus and lung, suggesting their involvement in the progression of these tumors. Oncogene (2001) 20, 6679 ± 6688.

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“…Some represent secreted or membranal proteins while others code for intracellular proteins. Proteins that are secreted, like HAI-2 and syndecan-1 (both of which are overexpressed in several cancers; Bayer-Garner et al, 2000;Dobra et al, 2000;Itoh et al, 2000;Kataoka et al, 2000), are suitable for the development of a noninvasive urine-based diagnostic test for TCC. Alternatively, an RT-PCR-based test on urine samples may be developed for genes coding for intracellular proteins, since the transitional epithelium cells are exfoliated in the urine in both normal and disease conditions (Rotem et al, 2000).…”

Section: Discussionmentioning

confidence: 99%