Expression of thrombospondin-1 by tumor cells in patient-derived ovarian carcinoma xenografts

Pinessi, Denise; Ostano, Paola; Borsotti, Patrizia; Bello, Ezia; Guffanti, Federica; Bizzaro, Francesca; Frapolli, Roberta; Bani, Maria Rosa; Chiorino, Giovanna; Taraboletti, Giulia; Resovi, Andrea

doi:10.3109/03008207.2015.1045065

Cited by 11 publications

(8 citation statements)

References 48 publications

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“…TSP-1 was also reported to contribute to metastatic spread by promoting tumor cell emboli formation ( Incardona et al, 1995 ). In recent years, an increasing number of studies have tended to present TSP-1 as a poor prognosis and recurrence marker in many cancer types including glioma ( Perez-Janices et al, 2015 ), melanoma ( Borsotti et al, 2015 ) as well as ovarian and pancreatic carcinomas ( Lyu et al, 2013 ; Nie et al, 2014 ; Pinessi et al, 2015 ). Among TSP-1 ligands, CD36 and CD47 cell-surface receptors act as key integrators of multiple signals regulating tumor growth and dissemination both positively and negatively.…”

Section: Tsp-1: a Main Actor Within Tumor Microenvironmentmentioning

confidence: 99%

“…Indeed, its ability to interact with multiple ligands enables TSP-1 to regulate a wide range of processes such as tumor cell adhesion ( Li et al, 2006 ), proliferation ( Sick et al, 2011 ), survival or apoptosis ( Manna and Frazier, 2004 ; Saumet et al, 2005 ; Rath et al, 2006a , b ), tumor invasion and metastatic dissemination ( Jayachandran et al, 2014 ; Borsotti et al, 2015 ), inflammation, immune response ( Grimbert et al, 2006 ) and response to treatment ( Lih et al, 2006 ; Bi et al, 2014 ). Such pleiotropic effects may be governed by TSP-1 concentration as well as by its origin, whether it originates from tumor cells or the stroma compartment ( Pinessi et al, 2015 ). Reverse responses may also be observed depending on the cancer type.…”

Section: Tsp-1: a Main Actor Within Tumor Microenvironmentmentioning

confidence: 99%

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Original insights on thrombospondin-1-related antireceptor strategies in cancer

et al. 2015

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Thrombospondin-1 (TSP-1) is a large matricellular glycoprotein known to be overexpressed within tumor stroma in several cancer types. While mainly considered as an endogenous angiogenesis inhibitor, TSP-1 exhibits multifaceted functionalities in a tumor context depending both on TSP-1 concentration as well as differential receptor expression by cancer cells and on tumor-associated stromal cells. Besides, the complex modular structure of TSP-1 along with the wide variety of its soluble ligands and membrane receptors considerably increases the complexity of therapeutically targeting interactions involving TSP-1 ligation of cell-surface receptors. Despite the pleiotropic nature of TSP-1, many different antireceptor strategies have been developed giving promising results in preclinical models. However, transition to clinical trials often led to nuanced outcomes mainly due to frequent severe adverse effects. In this review, we will first expose the intricate and even sometimes opposite effects of TSP-1-related signaling on tumor progression by paying particular attention to modulation of angiogenesis and tumor immunity. Then, we will provide an overview of current developments and prospects by focusing particularly on the cell-surface molecules CD47 and CD36 that function as TSP-1 receptors; including antibody-based approaches, therapeutic gene modulation and the use of peptidomimetics. Finally, we will discuss original approaches specifically targeting TSP-1 domains, as well as innovative combination strategies with a view to producing an overall anticancer response.

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Section: Tsp-1: a Main Actor Within Tumor Microenvironmentmentioning

confidence: 99%

Section: Tsp-1: a Main Actor Within Tumor Microenvironmentmentioning

confidence: 99%

Original insights on thrombospondin-1-related antireceptor strategies in cancer

et al. 2015

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“…It was revealed that desmin and H-caldesmon proteins were expressed in 8 models among 10 leiomyosarcomas PDX models, and the changes in vimentin and cytokeratin expression in carcinosarcomas PDX models varied over the generations [37]. Another related evidence revealed that thrombospondin-1 (TSP-1), regulating cell interaction with the microenvironment, was expressed in 10/11 ovarian cancer PDXs and upregulated in the homologous primary tumor, implying similar microenvironment of the PDX and original tumor [47]. On the other hand, it is also critical to illustrate the nonhuman component of expression data in PDX models.…”

Section: Phenotypic and Proteomic Featuresmentioning

confidence: 96%

The Application of Patient-Derived Xenograft Models in Gynecologic Cancers

et al. 2020

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Recently, due to the limitations of cell line models and animal models in the preclinical research with insufficient reflecting the physiological situation of humans, patient-derived xenograft (PDX) models of many cancers have been widely developed because of their better representation of the tumor heterogeneity and tumor microenvironment with retention of the cellular complexity, cytogenetics, and stromal architecture. PDX models now have been identified as a powerful tool for determining cancer characteristics, developing new treatment, and predicting drug efficacy. An increase in attempts to generate PDX models in gynecologic cancers has emerged in recent years to understand tumorigenesis. Hence, this review summarized the generation of PDX models and engraftment success of PDX models in gynecologic cancers. Furthermore, we illustrated the similarity between PDX model and original tumor, and described preclinical utilization of PDX models in gynecologic cancers. It would help supply better personalized therapy for gynecologic cancer patients.

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“…MYC is involved in cellular differentiation, growth and apoptosis, and plays a role in various human cancers [ 93 ]. The upregulation of the miR-17-92 cluster is associated with the downregulation of thrombospondin 1 (THBS1), an adhesive glycoprotein, which mediates cell–matrix and cell–cell interactions, with the potential to inhibit angiogenesis [ 94 ]. Therefore, the miR-17-92 cluster could be therapeutically targeted to lessen angiogenetic tumour growth in MYC-positive angiosarcomas.…”

Section: Micrornas In Human Soft Tissue Sarcomamentioning

confidence: 99%

MicroRNAs in Different Histologies of Soft Tissue Sarcoma: A Comprehensive Review

Smolle

Leithner

Posch

et al. 2017

IJMS

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Soft tissue sarcomas (STS) constitute a rare tumour entity comprising over 50 histological subtypes. MicroRNAs (miRNAs) are short non-protein coding RNA molecules that regulate gene expression by targeting the 3’-untranslated region of messenger RNAs. They are involved in a variety of human diseases, including malignancies, such as endometrial cancer, osteosarcoma, bronchial carcinoma and breast cancer. In STS, various miRNAs are differentially expressed, thus contributing to development, progression and invasion. Therefore, the aim of the present review is to summarise current knowledge on the role of miRNAs in STS. Furthermore, the potential role of miRNAs as diagnostic, prognostic and predictive biomarkers is discussed.

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Expression of thrombospondin-1 by tumor cells in patient-derived ovarian carcinoma xenografts

Abstract: Ovarian carcinoma PDX are a useful tool to investigate the relative contribution of stroma and tumor cells in the production of tumor associated factors, in relation to the tumor behavior, molecular properties and response to therapy.

Cited by 11 publications

References 48 publications

Original insights on thrombospondin-1-related antireceptor strategies in cancer

Original insights on thrombospondin-1-related antireceptor strategies in cancer

The Application of Patient-Derived Xenograft Models in Gynecologic Cancers

MicroRNAs in Different Histologies of Soft Tissue Sarcoma: A Comprehensive Review

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