A Role for Versican in the Development of Leiomyosarcoma

Keire, Paul; Bressler, Steven L.; Lemire, Joan M.; Edris, Badreddin; Rubin, Brian P.; Rahmani, Maziar; McManus, Bruce M.; Rijn, Matt van de; Wight, Thomas N.

doi:10.1074/jbc.m114.607168

Cited by 34 publications

(40 citation statements)

References 68 publications

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“…Given that these signaling pathways regulate tumorigenesis and that V3 expression in melanoma cells has been shown to significantly reduce tumorigenesis (16 -18), V3 may negatively impact tumorigenesis by affecting Wnt/␤-catenin and Notch signaling pathways. Recently, we have also found that negatively regulating versican in leiomyosarcoma cells significantly blocked tumorigenic potential when subcutaneously implanted into nude mice (53), which suggests V3 as a negative regulator of larger isoforms of versican may provide a novel anti-tumorigenic approach. A, changes in C3, Ccl2, Cxcl1, Ccl20, and Cxcl5 transcript levels were validated by qPCR using control LXSN or V3-expressing ASMCs cultured for 10 days.…”

Section: Discussionmentioning

confidence: 94%

Expression of V3 Versican by Rat Arterial Smooth Muscle Cells Promotes Differentiated and Anti-inflammatory Phenotypes

Kang

Barth

Sproul

et al. 2015

Journal of Biological Chemistry

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Background: Arterial smooth muscle cells (ASMCs) undergo phenotypic changes during pathophysiological processes. Results: V3 expression increases contractile SMC markers while decreasing a broad range of proinflammatory chemokines and transcription factors. Conclusion: V3 expression reprograms rat ASMCs promoting differentiated and anti-inflammatory phenotypes. Significance: Modifying ECM components via V3 expression could provide a potential therapeutic intervention against vascular and other diseases.

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Section: Discussionmentioning

confidence: 94%

Expression of V3 Versican by Rat Arterial Smooth Muscle Cells Promotes Differentiated and Anti-inflammatory Phenotypes

Kang

Barth

Sproul

et al. 2015

Journal of Biological Chemistry

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“…Versican expressed by some tumor cells affects their growth and metastatic potential. For example, versican is highly expressed in sporadic clear cell renal cell carcinoma inhibiting cell death [43] and in sarcomas promoting tumor cell proliferation and migration and increasing HA production [44, 45]. Abrogation of versican expression in T-anaplastic large cell lymphoma results in decreased levels of membrane type 1-MMP (MT1-MMP) and CD44 and marked suppression of T-cell adhesion and invasion [46].…”

Section: Versican: a Tumor Stroma-associated Proteoglycan In Breasmentioning

confidence: 99%

Insights into the key roles of proteoglycans in breast cancer biology and translational medicine

Theocharis

Skandalis

Neill

et al. 2015

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

114

127

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Proteoglycans control numerous normal and pathological processes, among which are morphogenesis, tissue repair, inflammation, vascularization and cancer metastasis. During tumor development and growth, proteoglycan expression is markedly modified in the tumor microenvironment. Altered expression of proteoglycans on tumor and stromal cell membranes affects cancer cell signaling, growth and survival, cell adhesion, migration and angiogenesis. Despite the high complexity and heterogeneity of breast cancer, the rapid evolution in our knowledge that proteoglycans are among the key players in the breast tumor microenvironment suggests their potential as pharmacological targets in this type of cancer. It has been recently suggested that pharmacological treatment may target proteoglycan metabolism, their utilization as targets for immunotherapy or their direct use as therapeutic agents. The diversity inherent in the proteoglycans that will be presented herein provides the potential for multiple layers of regulation of breast tumor behavior. This review summarizes recent developments concerning the biology of selected proteoglycans in breast cancer, and presents potential targeted therapeutic approaches based on their novel key roles in breast cancer.

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“…In previous studies [32], LMS cells were treated with individual in vitro transcribed siRNAs specifically directed and spaced along the length of versican mRNA. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) mRNA analyses revealed that the 5´-G1-directed siRNA was the most effective at inhibiting versican.…”

Section: Resultsmentioning

confidence: 99%

“…Leiomyosarcoma (LMS) cells, for example, produce a large amount of versican and, in previous experiments, we have shown that inhibiting versican synthesis in LMS cells inhibits both proliferation and tumor formation when these cells are injected into nude mice [32]. Correspondingly, we have found that the addition of exogenous versican restores the high proliferative rate of slow proliferating versican-depleted LMS cells while increasing migration and decreasing substrate adhesion [32]. …”

Section: Introductionmentioning

confidence: 99%

Inhibition of versican expression by siRNA facilitates tropoelastin synthesis and elastic fiber formation by human SK-LMS-1 leiomyosarcoma smooth muscle cells in vitro and in vivo

et al. 2016

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Versican is an extracellular matrix (ECM) molecule that interacts with other ECM components to influence ECM organization, stability, composition, and cell behavior. Versican is known to increase in a number of cancers, but little is known about how versican influences the amount and organization of the ECM components in the tumor microenvironment. In the present study, we modulated versican expression using siRNAs in the human leiomyosarcoma (LMS) smooth muscle cell line SK-LMS-1, and observed the formation of elastin and elastic fibers in vitro and also in vivo in a nude mouse tumor model. Constitutive siRNA-directed knockdown of versican in LMS cells resulted in increased levels of elastin, as shown by immunohistochemical staining of the cells in vitro, and by mRNA and protein analyses. Moreover, versican siRNA LMS cells, when injected into nude mice, generated smaller tumors that had significantly greater immunohistochemical and histochemical staining for elastin when compared to control tumors. Additionally, microarray analyses were used to determine the influence of versican isoform modulation on gene expression profiles, and to identify genes that influence and relate to the process of elastogenesis. cDNA microarray analysis and TaqMan low density array validation identified previously unreported genes associated with downregulation of versican and increased elastogenesis. These results highlight an important role for the proteoglycan versican in regulating the expression and assembly of elastin and the phenotype of LMS cells.

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A Role for Versican in the Development of Leiomyosarcoma

Cited by 34 publications

References 68 publications

Expression of V3 Versican by Rat Arterial Smooth Muscle Cells Promotes Differentiated and Anti-inflammatory Phenotypes

Expression of V3 Versican by Rat Arterial Smooth Muscle Cells Promotes Differentiated and Anti-inflammatory Phenotypes

Insights into the key roles of proteoglycans in breast cancer biology and translational medicine

Inhibition of versican expression by siRNA facilitates tropoelastin synthesis and elastic fiber formation by human SK-LMS-1 leiomyosarcoma smooth muscle cells in vitro and in vivo

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