Thrombospondin 1 promotes an aggressive phenotype through epithelial-to-mesenchymal transition in human melanoma

Jayachandran, Aparna; Anaka, Matthew; Prithviraj, Prashanth; Hudson, Chris; McKeown, Sonja J.; Lo, Pu-Han; Vella, Laura J.; Goding, Colin R.; Cebon, Jonathan; Behren, Andreas

doi:10.18632/oncotarget.2164

Cited by 127 publications

(125 citation statements)

References 65 publications

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“…Metastatic volume inside lungs is indicated at the right bottom of the picture over the last 2 years pointing out the contribution of TSP-1 in melanoma metastatic program. TSP-1 was indeed first described in 2014 as promoting an epithelial-to-mesenchymal transition (EMT) in human melanoma cells [10]. At the same time, Borsotti et al identified TSP-1 as a main actor of a motility and metastatic program in melanoma [13].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, two research teams independently reported THBS1 gene expression to be elevated in chemoresistant and motile melanoma cells [10,13], thus supporting the concept of a TSP-1-driven invasion program in melanoma. By overlapping gene expression data with PPI information registered in the human protein reference database (HPRD) [21], we here demonstrate that a THBS1-centered whole network of genes encoding for ECM proteins and receptors cross-interacting with each other is actually overexpressed in melanoma (Fig.…”

Section: Thbs1 Interaction Network Is Overexpressed In Malignant Melamentioning

confidence: 91%

“…V600E BRAF allowed compelling clinical outcomes, resistance acquisition considerably limits long-term benefits with metastatic spread remaining a main therapeutic challenge [8,9]. Recent work on patient-derived melanoma cells underlined a role for TSP-1 in the acquisition of an aggressive phenotype by promoting epithelial-to-mesenchymal transition (EMT), therefore making TSP-1 a putative poor prognosis and recurrence marker [10]. Among its various cell-surface receptors, CD47 appears a key signaling integrator of TSP-1-mediated modulation of tumor progression [11,12].…”

Section: Introductionmentioning

confidence: 99%

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Matricellular TSP-1 as a target of interest for impeding melanoma spreading: towards a therapeutic use for TAX2 peptide

Jeanne

Boulagnon‐Rombi

Devy

et al. 2016

Clin Exp Metastasis

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Thrombospondin-1 (TSP-1) is a matricellular glycoprotein known for being highly expressed within a tumor microenvironment, where it promotes an aggressive phenotype particularly by interacting with the CD47 cell-surface receptor. While it originates from the stromal compartment in many malignancies, melanoma is an exception as invasive and metastatic melanoma cells overexpress TSP-1. We recently demonstrated that a new molecular agent that selectively prevents TSP-1 binding to CD47, called TAX2, exhibits anti-cancer properties when administered systemically by decreasing viable tumor tissue within subcutaneous B16 melanoma allografts. At the same time, emerging evidence was published suggesting a contribution of TSP-1 in melanoma metastatic dissemination and resistance to treatment. Through a comprehensive systems biology approach based on multiple genomics and proteomics databases analyses, we first identified a TSP-1-centered interaction network that is overexpressed in metastatic melanoma. Then, we investigated the effects of disrupting TSP-1:CD47 interaction in A375 human malignant melanoma xenografts. In this model, TAX2 systemic administrations induce tumor necrosis by decreasing intra-tumoral blood flow, while concomitantly making tumors less infiltrative. Besides, TAX2 treatment also drastically inhibits B16F10 murine melanoma cells metastatic dissemination and growth in a syngeneic experimental model of lung metastasis, as demonstrated by histopathological analyses as well as longitudinal and quantitative µCT follow-up of metastatic progression. Altogether, the results obtained by combining bioinformatics and preclinical studies strongly suggest that targeting TSP-1/CD47 axis may represent a valuable therapeutic alternative for hampering melanoma spreading.

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Section: Discussionmentioning

confidence: 99%

Section: Thbs1 Interaction Network Is Overexpressed In Malignant Melamentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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Matricellular TSP-1 as a target of interest for impeding melanoma spreading: towards a therapeutic use for TAX2 peptide

Jeanne

Boulagnon‐Rombi

Devy

et al. 2016

Clin Exp Metastasis

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“…Epithelial-to-mesenchymal transition (EMT) is a cellular process during which epithelial cells undergo a phenotypic switch to become more aggressive and motile mesenchymal cells [62] . The process of EMT is also a major contributor for metastasis and drug resistance [61] .…”

Section: Epithelial-to-mesenchymal Transitionmentioning

confidence: 99%

Exosome-based liquid biopsy in the management of hepatocellular carcinoma

Jayachandran¹,

Manda²,

Shrestha³

et al. 2018

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Hepatocellular carcinoma (HCC) commonly presents at an advanced stage due to the lack of efficient early screening tools. Early, non-invasive biomarkers useful in the diagnosis and prognosis of HCC would be of significant benefit for HCC management. Development of exosome-based liquid biopsy as a non-invasive method for the management of HCC has gained much traction. Exosomes are small membranous vesicles secreted by most cell types including HCC cells. Exosomes serve as couriers for the intercellular transfer of important biomolecules, including, protein, nucleic acids and lipids to nearby and distant cells in the body. The molecular cargos carried by exosome have been described to play significant roles in cancer progression. Herein, we will dissect how HCC-derived exosomes confer aggressive traits such as tumour growth, invasion, immune remodelling and drug resistance to HCC cells. We review the current literature concerning exosomes as biomarkers in a diagnostic setting, evaluating their prognostic, predictive and monitoring capabilities. This review will highlight and discuss emerging research in the utility of exosome-based liquid biopsies therapeutic tools in HCC management. Here we will also focus on advances in exosome biology in preclinical studies.

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“…33 In addition, we found genes that have been shown to be important in the epithelial-mesenchymal transition (PVRL1, THBS1, MMP-13). [34][35][36] Given the background of these genes, we proposed that the SSEA-1C cell population may have a slightly different identity expressing higher levels of genes found in mesenchymal stem cells and mesoderm/mesendoderm.…”

Section: Enhanced Reprogramming Could Be Determined In Single Danish mentioning

confidence: 99%

Identification of SSEA-1 expressing enhanced reprogramming (SEER) cells in porcine embryonic fibroblasts

et al. 2017

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Previous research has shown that a subpopulation of cells within cultured human dermal fibroblasts, termed multilineage-differentiating stress enduring (Muse) cells, are preferentially reprogrammed into induced pluripotent stem cells. However, controversy exists over whether these cells are the only cells capable of being reprogrammed from a heterogeneous population of fibroblasts. Similarly, there is little research to suggest such cells may exist in embryonic tissues or other species. To address if such a cell population exists in pigs, we investigated porcine embryonic fibroblast populations (pEFs) and identified heterogeneous expression of several key cell surface markers. Strikingly, we discovered a small population of stage-specific embryonic antigen 1 positive cells (SSEA-1C) in Danish Landrace and G€ ottingen minipig pEFs, which were absent in the Yucatan pEFs. Furthermore, reprogramming of SSEA-1C sorted pEFs led to higher reprogramming efficiency. Subsequent transcriptome profiling of the SSEA-1C vs. the SSEA-1neg cell fraction revealed highly comparable gene signatures. However several genes that were found to be upregulated in the SSEA-1C cells were similarly expressed in mesenchymal stem cells (MSCs). We therefore termed these cells SSEA-1 Expressing Enhanced Reprogramming (SEER) cells. Interestingly, SEER cells were more effective at differentiating into osteocytes and chondrocytes in vitro. We conclude that SEER cells are more amenable for reprogramming and that the expression of mesenchymal stem cell genes is advantageous in the reprogramming process. This data provides evidence supporting the elite theory and helps to delineate which cell types and specific genes are important for reprogramming in the pig.

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Thrombospondin 1 promotes an aggressive phenotype through epithelial-to-mesenchymal transition in human melanoma

Cited by 127 publications

References 65 publications

Matricellular TSP-1 as a target of interest for impeding melanoma spreading: towards a therapeutic use for TAX2 peptide

Matricellular TSP-1 as a target of interest for impeding melanoma spreading: towards a therapeutic use for TAX2 peptide

Exosome-based liquid biopsy in the management of hepatocellular carcinoma

Identification of SSEA-1 expressing enhanced reprogramming (SEER) cells in porcine embryonic fibroblasts

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