Thrombospondin-1 Triggers Cell Migration and Development of Advanced Prostate Tumors

Firlej, Virginie; Mathieu, Jacques; Gilbert, Cristèle; Lemonnier, Loïc; Nakhlé, Jessica; Gallou-Kabani, Catherine; Guarmit, Basma; Morin, Aurélie; Prevarskaya, Natalia; Delongchamps, Nicolas Barry; Cabon, Florence

doi:10.1158/0008-5472.can-11-0833

Cited by 87 publications

(88 citation statements)

References 52 publications

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“…Interestingly, several earlier reports suggested that TSP-1 was also able to promote tumor cell migration in a variety of cancers such as melanoma and prostate cancer 14,17 . Both TSP-1 and CD36 are also detected in normal, hyperplasic, and neoplastic human breast tissue 6,34,35 .…”

Section: Discussionmentioning

confidence: 99%

Thrombospondin-1 Modulates Actin Filament Remodeling and Cell Motility in Mouse Mammary Tumor cells in Vitro

et al. 2014

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It is well established that the secretion of thrombospondin-1 (TSP-1) by activated stromal cells and its accumulation in the tumor microenvironment during dysplasia inhibits primary tumor growth through inhibition of angiogenesis. This inhibitory function of TSP-1 is actuated either by inhibiting MMP9 activation and the release of VEGF from extracellular matrix or by an interaction with CD36 on the surface of endothelial cells resulting in an increase in apoptosis. In contrast, several published articles have also shown that as tumor cells become more invasive and enter the early stage of carcinoma, they up-regulate TSP-1 expression, which may promote invasion and migration. In our in vivo studies using the polyoma middle T antigen (PyT) transgenic mouse model of breast cancer, we observed that the absence of TSP-1 significantly increased the growth of primary tumors, but delayed metastasis to the lungs. In this study, we propose a mechanism for the promigratory function of TSP-1 in mouse mammary tumor cells in vitro. We demonstrate the correlations between expression of TSP-1 and its receptor integrin α3β1, which is considered a promigratory protein in cancer cells. In addition we propose that binding of TSP-1 to integrin α3β1 is important for mediating actin filament polymerization and therefore, cell motility. These findings can help explain the dual functionality of TSP-1 in cancer progression.

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Section: Discussionmentioning

confidence: 99%

Thrombospondin-1 Modulates Actin Filament Remodeling and Cell Motility in Mouse Mammary Tumor cells in Vitro

et al. 2014

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“…However, multiple receptors engaged by TSP-1 makes this function differ based on cell types such that an inhibitory effect on cellular migration is reported in the case of vascular endothelial cells 31 and dendritic cells 32 , while promotion of migration is noted in the case of neural crest cells 33 , fibroblasts 34 , corneal endothelial cells 35 and T cells 36 . In the case of tumor cells migration is correlated with metastasis; with inhibition reported in some tumor cells 37 and tumor progression in others 38, 39 . These differences are partly due to the fact that tumor cell migration is downstream of other functions influenced by TSP-1 such as activation of latent TGF-β, inhibition of angiogenesis or up-regulation of matrix metalloproteinases 40 .…”

Section: Introductionmentioning

confidence: 99%

Matricellular Protein Thrombospondins: Influence on Ocular Angiogenesis, Wound Healing and Immuneregulation

Masli

Cursiefen

Zieske

2014

Current Eye Research

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Thrombospondins are a family of large multi-domain glycoproteins described as matricelluar proteins based on their ability to interact with a broad range of receptors, matrix molecules, growth factors or proteases and to modulate array of cellular functions including intracellular signaling, proliferation and migration. Two members of the thrombospondin family, thrombospondin 1 (TSP1) and thrombospondin 2 (TSP2) are studied extensively to determine their structure and function. While expressed at low levels in normal adult tissues their increased expression is seen predominantly in response to cellular perturbations. Despite structural similarities a notable functional difference between TSP1 and TSP2 includes the ability of former to activate of latent TGF-β and its competitive inhibition by the latter. Both these thrombospondins are reported to play important roles in TGF-β rich ocular environment with most reports related to TSP1. Expressed by many ocular cell types and detectable in the aqueous and vitreous humor TSP1 and TSP2 influence many cellular interactions in the eye such as angiogenesis, cell migration, wound healing, TGF-β activation and regulation of inflammatory immune responses. Together these processes are known to contribute to the immune privilege status of the eye. Emerging roles of TSP1 and TSP2 in ocular functions and pathology are reviewed here.

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“…THBS1 was decreased 2 folds after fascin was knocked down in the data that applied in this study. Previous results show that THBS1 is a potent stimulator of prostate tumor cell migration (Firlej et al, 2011). It was reported that loss of THBS1 expression was also significantly associated with distal location, vascular invasion and distant metastasis in gastric cancer and with unfavourable histological grade and shorter overall survival in penile squamous cell carcinoma (Miyamoto et al, 2007;Guerrero et al, 2008).…”

Section: Discussionmentioning

confidence: 94%

Comprehensive Bioinformation Analysis of the MRNA Profile of Fascin Knockdown in Esophageal Squamous Cell Carcinoma

Wu¹,

Luo²,

Li³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Fascin, an actin-bundling protein forming actin bundles including filopodia and stress fibers, is overexpressed in multiple human epithelial cancers including esophageal squamous cell carcinoma (ESCC). Previously we conducted a microarray experiment to analyze fascin knockdown by RNAi in ESCC. Method: In this study, the differentially expressed genes from mRNA expression profilomg of fascin knockdown were analyzed by multiple bioinformatics methods for a comprehensive understanding of the role of fascin. Results: Gene Ontology enrichment found terms associated with cytoskeleton organization, including cell adhesion, actin filament binding and actin cytoskeleton, which might be related to fascin function. Except GO categories, the differentially expressed genes were annotated by 45 functional categories from the Functional Annotation Chart of DAVID. Subpathway analysis showed thirty-nine pathways were disturbed by the differentially expressed genes, providing more detailed information than traditional pathway enrichment analysis. Two subpathways derivated from regulation of the actin cytoskeleton were shown. Promoter analysis results indicated distinguishing sequence patterns and transcription factors in response to the co-expression of downregulated or upregulated differentially expressed genes. MNB1A, c-ETS, GATA2 and Prrx2 potentially regulate the transcription of the downregulated gene set, while Arnt-Ahr, ZNF42, Ubx and TCF11-MafG might co-regulate the upregulated genes. Conclusions: This multiple bioinformatic analysis helps provide a comprehensive understanding of the roles of fascin after its knockdown in ESCC.

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Thrombospondin-1 Triggers Cell Migration and Development of Advanced Prostate Tumors

Cited by 87 publications

References 52 publications

Thrombospondin-1 Modulates Actin Filament Remodeling and Cell Motility in Mouse Mammary Tumor cells in Vitro

Thrombospondin-1 Modulates Actin Filament Remodeling and Cell Motility in Mouse Mammary Tumor cells in Vitro

Matricellular Protein Thrombospondins: Influence on Ocular Angiogenesis, Wound Healing and Immuneregulation

Comprehensive Bioinformation Analysis of the MRNA Profile of Fascin Knockdown in Esophageal Squamous Cell Carcinoma

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