LIVIVO - Search results -

Search results

Result 1 - 10 of total 62

Search options

Article ; Online: Controlled extracellular proteolysis of thrombospondins.

Carminati, Laura / Carlessi, Elena / Longhi, Elisa / Taraboletti, Giulia

Matrix biology : journal of the International Society for Matrix Biology

2023 Volume 119, Page(s) 82–100

Abstract: Limited proteolysis of thrombospondins is a powerful mechanism to ensure dynamic tuning of their activities in the extracellular space. Thrombospondins are multifunctional matricellular proteins composed of multiple domains, each with a specific pattern ... ...

Abstract	Limited proteolysis of thrombospondins is a powerful mechanism to ensure dynamic tuning of their activities in the extracellular space. Thrombospondins are multifunctional matricellular proteins composed of multiple domains, each with a specific pattern of interactions with cell receptors, matrix components and soluble factors (growth factors, cytokines and proteases), thus with different effects on cell behavior and responses to changes in the microenvironment. Therefore, the proteolytic degradation of thrombospondins has multiple functional consequences, reflecting the local release of active fragments and isolated domains, exposure or disruption of active sequences, altered protein location, and changes in the composition and function of TSP-based pericellular interaction networks. In this review current data from the literature and databases is employed to provide an overview of cleavage of mammalian thrombospondins by different proteases. The roles of the fragments generated in specific pathological settings, with particular focus on cancer and the tumor microenvironment, are discussed.
MeSH term(s)	Animals ; Humans ; Thrombospondins/genetics ; Thrombospondins/metabolism ; Proteolysis ; Neoplasms/metabolism ; Peptide Hydrolases/metabolism ; Tumor Microenvironment ; Extracellular Matrix/metabolism ; Mammals/metabolism
Chemical Substances	Thrombospondins ; Peptide Hydrolases (EC 3.4.-)
Language	English
Publishing date	2023-03-30
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1183793-7
ISSN	1569-1802 ; 0945-053X
ISSN (online)	1569-1802
ISSN	0945-053X
DOI	10.1016/j.matbio.2023.03.011
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1694: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Thrombospondin-1 in drug activity and tumor response to therapies.

Longhi, Elisa / Carminati, Laura / Carlessi, Elena / Belotti, Dorina / Taraboletti, Giulia

Seminars in cell & developmental biology

2023 Volume 155, Issue Pt B, Page(s) 45–51

Abstract: Thrombospondins (TSPs) have numerous different roles in cancer, regulating the behavior of cancer cells and non-neoplastic cells, and defining the responses of tumor cells to environmental changes, thorough their ability to orchestrate cellular and ... ...

Abstract	Thrombospondins (TSPs) have numerous different roles in cancer, regulating the behavior of cancer cells and non-neoplastic cells, and defining the responses of tumor cells to environmental changes, thorough their ability to orchestrate cellular and molecular interactions in the tumor microenvironment (TME). As a result of these activities, TSPs can also control drug delivery and activity, tumor response and resistance to therapies, with different outcomes depending on the nature of TSP-interacting cell types, receptors, and ligands, in a highly context-dependent manner. This review, focusing primarily on TSP-1, discusses the effects of TSPs on tumor response to chemotherapy, antiangiogenic, low-dose metronomic chemotherapy, immunotherapy, and radiotherapy, by analyzing TSP activity on different cell compartments - tumor cells, vascular endothelial cells and immune cells. We review evidence of the value of TSPs, specifically TSP-1 and TSP-2, as biomarkers of prognosis and tumor response to therapy. Finally, we examine possible approaches to develop TSP-based compounds as therapeutic tools to potentiate the efficacy of anticancer therapy.
MeSH term(s)	Humans ; Thrombospondin 1 ; Endothelial Cells/metabolism ; Thrombospondins/metabolism ; Neoplasms/drug therapy ; Immunotherapy ; Tumor Microenvironment
Chemical Substances	Thrombospondin 1 ; Thrombospondins
Language	English
Publishing date	2023-07-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1312473-0
ISSN	1096-3634 ; 1084-9521
ISSN (online)	1096-3634
ISSN	1084-9521
DOI	10.1016/j.semcdb.2023.06.009
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2918: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Thrombospondins in bone remodeling and metastatic bone disease.

Carminati, Laura / Taraboletti, Giulia

American journal of physiology. Cell physiology

2020 Volume 319, Issue 6, Page(s) C980–C990

Abstract: Thrombospondins (TSPs) are a family of five multimeric matricellular proteins. Through a wide range of interactions, TSPs play pleiotropic roles in embryogenesis and in tissue remodeling in adult physiology as well as in pathological conditions, ... ...

Abstract	Thrombospondins (TSPs) are a family of five multimeric matricellular proteins. Through a wide range of interactions, TSPs play pleiotropic roles in embryogenesis and in tissue remodeling in adult physiology as well as in pathological conditions, including cancer development and metastasis. TSPs are active in bone remodeling, the process of bone resorption (osteolysis) and deposition (osteogenesis) that maintains bone homeostasis. TSPs are particularly involved in aberrant bone remodeling, including osteolytic and osteoblastic skeletal cancer metastasis, frequent in advanced cancers such as breast and prostate carcinoma. TSPs are major players in the bone metastasis microenvironment, where they finely tune the cross talk between tumor cells and bone resident cells in the metastatic niche. Each TSP family member has different effects on the differentiation and activity of bone cells-including the bone-degrading osteoclasts and the bone-forming osteoblasts-with different outcomes on the development and growth of osteolytic and osteoblastic metastases. Here, we overview the involvement of TSP family members in the bone tissue microenvironment, focusing on their activity on osteoclasts and osteoblasts in bone remodeling, and present the evidence to date of their roles in bone metastasis establishment and growth.
MeSH term(s)	Animals ; Bone Neoplasms/metabolism ; Bone Neoplasms/pathology ; Bone Remodeling/physiology ; Humans ; Osteoblasts/metabolism ; Osteoblasts/pathology ; Osteoclasts/metabolism ; Osteoclasts/pathology ; Osteogenesis/physiology ; Thrombospondins/metabolism
Chemical Substances	Thrombospondins
Language	English
Publishing date	2020-09-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	392098-7
ISSN	1522-1563 ; 0363-6143
ISSN (online)	1522-1563
ISSN	0363-6143
DOI	10.1152/ajpcell.00383.2020
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.89: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Alternative Vascularization Mechanisms in Tumor Resistance to Therapy.

Belotti, Dorina / Pinessi, Denise / Taraboletti, Giulia

Cancers

2021 Volume 13, Issue 8

Abstract: Blood vessels in tumors are formed through a variety of different mechanisms, each generating vessels with peculiar structural, molecular, and functional properties. This heterogeneity has a major impact on tumor response or resistance to antineoplastic ... ...

Abstract	Blood vessels in tumors are formed through a variety of different mechanisms, each generating vessels with peculiar structural, molecular, and functional properties. This heterogeneity has a major impact on tumor response or resistance to antineoplastic therapies and is now emerging as a promising target for strategies to prevent drug resistance and improve the distribution and efficacy of antineoplastic treatments. This review presents evidence of how different mechanisms of tumor vessel formation (vasculogenesis, glomeruloid proliferation, intussusceptive angiogenesis, vasculogenic mimicry, and vessel co-option) affect tumor responses to antiangiogenic and antineoplastic therapies, but also how therapies can promote alternative mechanisms of vessel formation, contributing to tumor recurrence, malignant progression, and acquired drug resistance. We discuss the possibility of tailoring treatment strategies to overcome vasculature-mediated drug resistance or to improve drug distribution and efficacy.
Language	English
Publishing date	2021-04-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13081912
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Inhibition of FGFR Signaling by Targeting FGF/FGFR Extracellular Interactions: Towards the Comprehension of the Molecular Mechanism through NMR Approaches.

Pagano, Katiuscia / Longhi, Elisa / Molinari, Henriette / Taraboletti, Giulia / Ragona, Laura

International journal of molecular sciences

2022 Volume 23, Issue 18

Abstract: NMR-based approaches play a pivotal role in providing insight into molecular recognition mechanisms, affording the required atomic-level description and enabling the identification of promising inhibitors of protein-protein interactions. The aberrant ... ...

Abstract	NMR-based approaches play a pivotal role in providing insight into molecular recognition mechanisms, affording the required atomic-level description and enabling the identification of promising inhibitors of protein-protein interactions. The aberrant activation of the fibroblast growth factor 2 (FGF2)/fibroblast growth factor receptor (FGFR) signaling pathway drives several pathologies, including cancer development, metastasis formation, resistance to therapy, angiogenesis-driven pathologies, vascular diseases, and viral infections. Most FGFR inhibitors targeting the intracellular ATP binding pocket of FGFR have adverse effects, such as limited specificity and relevant toxicity. A viable alternative is represented by targeting the FGF/FGFR extracellular interactions. We previously identified a few small-molecule inhibitors acting extracellularly, targeting FGFR or FGF. We have now built a small library of natural and synthetic molecules that potentially act as inhibitors of FGF2/FGFR interactions to improve our understanding of the molecular mechanisms of inhibitory activity. Here, we provide a comparative analysis of the interaction mode of small molecules with the FGF2/FGFR complex and the single protein domains. DOSY and residue-level NMR analysis afforded insights into the capability of the potential inhibitors to destabilize complex formation, highlighting different mechanisms of inhibition of FGF2-induced cell proliferation.
MeSH term(s)	Adenosine Triphosphate/pharmacology ; Comprehension ; Fibroblast Growth Factor 2/pharmacology ; Fibroblast Growth Factors/metabolism ; Humans ; Neoplasms/metabolism ; Receptors, Fibroblast Growth Factor/metabolism ; Signal Transduction
Chemical Substances	Receptors, Fibroblast Growth Factor ; Fibroblast Growth Factor 2 (103107-01-3) ; Fibroblast Growth Factors (62031-54-3) ; Adenosine Triphosphate (8L70Q75FXE)
Language	English
Publishing date	2022-09-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms231810860
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Identification of a novel extracellular inhibitor of FGF2/FGFR signaling axis by combined virtual screening and NMR spectroscopy approach.

Pagano, Katiuscia / Listro, Roberta / Linciano, Pasquale / Rossi, Daniela / Longhi, Elisa / Taraboletti, Giulia / Molinari, Henriette / Collina, Simona / Ragona, Laura

Bioorganic chemistry

2023 Volume 136, Page(s) 106529

Abstract: The aberrant activation of the fibroblast growth factor 2 (FGF2)/fibroblast growth factor receptor (FGFR) signalling pathway drives severe pathologies, including cancer development and angiogenesis-driven pathologies. The perturbation of the FGF2/FGFR ... ...

Abstract	The aberrant activation of the fibroblast growth factor 2 (FGF2)/fibroblast growth factor receptor (FGFR) signalling pathway drives severe pathologies, including cancer development and angiogenesis-driven pathologies. The perturbation of the FGF2/FGFR axis via extracellular allosteric small inhibitors is a promising strategy for developing FGFR inhibitors with improved safety and efficacy for cancer treatment. We have previously investigated the role of new extracellular inhibitors, such as rosmarinic acid (RA), which bind the FGFR-D2 domain and directly compete with FGF2 for the same binding site, enabling the disruption of the functional FGF2/FGFR interaction. To select ligands for the previously identified FGF2/FGFR RA binding site, NMR data-driven virtual screening has been performed on an in-house library of non-commercial small molecules and metabolites. A novel drug-like compound, a resorcinol derivative named RBA4 has been identified. NMR interaction studies demonstrate that RBA4 binds the FGF2/FGFR complex, in agreement with docking prediction. Residue-level NMR perturbations analysis highlights that the mode of action of RBA4 is similar to RA in terms of its ability to target the FGF2/FGFR-D2 complex, inducing perturbations on both proteins and triggering complex dissociation. Biological assays proved that RBA4 inhibited FGF2 proliferative activity at a level comparable to the previously reported natural product, RA. Identification of RBA4 chemical groups involved in direct interactions represents a starting point for further optimization of drug-like extracellular inhibitors with improved activity.
MeSH term(s)	Humans ; Fibroblast Growth Factor 2/antagonists & inhibitors ; Magnetic Resonance Spectroscopy ; Neoplasms ; Receptors, Fibroblast Growth Factor/antagonists & inhibitors ; Receptors, Fibroblast Growth Factor/metabolism ; Signal Transduction ; Resorcinols/chemistry ; Resorcinols/pharmacology
Chemical Substances	Fibroblast Growth Factor 2 (103107-01-3) ; Receptors, Fibroblast Growth Factor ; Resorcinols
Language	English
Publishing date	2023-04-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120080-x
ISSN	1090-2120 ; 0045-2068
ISSN (online)	1090-2120
ISSN	0045-2068
DOI	10.1016/j.bioorg.2023.106529
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4207: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Fibronectin fragments generated by pancreatic trypsin act as endogenous inhibitors of pancreatic tumor growth.

Resovi, Andrea / Persichitti, Perla / Brunelli, Laura / Minoli, Lucia / Borsotti, Patrizia / Garattini, Giulia / Tironi, Matteo / Dugnani, Erica / Redegalli, Miriam / De Simone, Giulia / Pastorelli, Roberta / Bani, Maria Rosa / Piemonti, Lorenzo / Mosher, Deane F / Giavazzi, Raffaella / Taraboletti, Giulia / Belotti, Dorina

Journal of experimental & clinical cancer research : CR

2023 Volume 42, Issue 1, Page(s) 201

Abstract: Background: The pancreatic microenvironment has a defensive role against cancer but it can acquire tumor-promoting properties triggered by multiple mechanisms including alterations in the equilibrium between proteases and their inhibitors. The ... ...

Abstract	Background: The pancreatic microenvironment has a defensive role against cancer but it can acquire tumor-promoting properties triggered by multiple mechanisms including alterations in the equilibrium between proteases and their inhibitors. The identification of proteolytic events, targets and pathways would set the basis for the design of new therapeutic approaches. Methods and results: Here we demonstrate that spheroids isolated from human and murine healthy pancreas and co-transplanted orthotopically with pancreatic ductal adenocarcinoma (PDAC) in mouse pancreas inhibited tumor growth. The effect was mediated by trypsin-generated fibronectin (FN) fragments released by pancreatic spheroids. Tumor inhibition was observed also in a model of acute pancreatitis associated with trypsin activation. Mass spectrometry proteomic analysis of fragments and mAb against different FN epitopes identified the FN type III domain as responsible for the activity. By inhibiting integrin α5β1, FAK and FGFR1 signaling, the fragments induced tumor cell detachment and reduced cell proliferation. Consistent with the mutual relationship between the two pathways, FGF2 restored both FGFR1 and FAK signaling and promoted PDAC cell adhesion and proliferation. FAK and FGFR inhibitors additively inhibited PDAC growth in vitro and in orthotopic in vivo models. Conclusions: This study identifies a novel role for pancreatic trypsin and fibronectin cleavage as a mechanism of protection against cancer by the pancreatic microenvironment. The finding of a FAK-FGFR cross-talk in PDAC support the combination of FAK and FGFR inhibitors for PDAC treatment to emulate the protective effect of the normal pancreas against cancer.
MeSH term(s)	Animals ; Humans ; Mice ; Acute Disease ; Carcinoma, Pancreatic Ductal/pathology ; Cell Line, Tumor ; Cell Proliferation ; Fibronectins/metabolism ; Pancreas/pathology ; Pancreatic Neoplasms/pathology ; Pancreatitis ; Proteomics ; Trypsin/metabolism ; Tumor Microenvironment ; Pancreatic Neoplasms
Chemical Substances	Fibronectins ; Trypsin (EC 3.4.21.4)
Language	English
Publishing date	2023-08-09
Publishing country	England
Document type	Journal Article
ZDB-ID	803138-1
ISSN	1756-9966 ; 0392-9078
ISSN (online)	1756-9966
ISSN	0392-9078
DOI	10.1186/s13046-023-02778-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2065: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Molecular Basis of the Antiangiogenic Action of Rosmarinic Acid, a Natural Compound Targeting Fibroblast Growth Factor-2/FGFR Interactions.

Pagano, Katiuscia / Carminati, Laura / Tomaselli, Simona / Molinari, Henriette / Taraboletti, Giulia / Ragona, Laura

Chembiochem : a European journal of chemical biology

2020 Volume 22, Issue 1, Page(s) 160–169

Abstract: Fibroblast growth factor (FGF2)/fibroblast growth factor receptor (FGFR) signalling plays a major role both in physiology and in several pathologies, including cancer development, metastasis formation and resistance to therapy. The development of small ... ...

Abstract	Fibroblast growth factor (FGF2)/fibroblast growth factor receptor (FGFR) signalling plays a major role both in physiology and in several pathologies, including cancer development, metastasis formation and resistance to therapy. The development of small molecules, acting extracellularly to target FGF2/FGFR interactions, has the advantage of limiting the adverse effects associated with current intracellular FGFR inhibitors. Herein, we discuss the ability of the natural compound rosmarinic acid (RA) to induce FGF2/FGFR complex dissociation. The molecular-level description of the FGF2/FGFR/RA system, by NMR spectroscopy and docking, clearly demonstrates that RA binds to the FGFR-D2 domain and directly competes with FGF2 for the same binding site. Direct and allosteric perturbations combine to destabilise the complex. The proposed molecular mechanism is validated by cellular studies showing that RA inhibits FGF2-induced endothelial cell proliferation and FGFR activation. Our results can serve as the basis for the development of new extracellular inhibitors of the FGF/FGFR pathways.
MeSH term(s)	Angiogenesis Inhibitors/chemistry ; Angiogenesis Inhibitors/pharmacology ; Animals ; Biological Products/chemistry ; Biological Products/pharmacology ; Cattle ; Cell Proliferation/drug effects ; Cells, Cultured ; Cinnamates/chemistry ; Cinnamates/pharmacology ; Depsides/chemistry ; Depsides/pharmacology ; Fibroblast Growth Factor 2/antagonists & inhibitors ; Fibroblast Growth Factor 2/chemistry ; Fibroblast Growth Factor 2/metabolism ; Molecular Docking Simulation ; Phosphorylation/drug effects ; Receptors, Fibroblast Growth Factor/antagonists & inhibitors ; Receptors, Fibroblast Growth Factor/chemistry ; Receptors, Fibroblast Growth Factor/metabolism ; Rosmarinic Acid
Chemical Substances	Angiogenesis Inhibitors ; Biological Products ; Cinnamates ; Depsides ; Receptors, Fibroblast Growth Factor ; Fibroblast Growth Factor 2 (103107-01-3)
Language	English
Publishing date	2020-11-06
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2020469-3
ISSN	1439-7633 ; 1439-4227
ISSN (online)	1439-7633
ISSN	1439-4227
DOI	10.1002/cbic.202000610
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Details ▾
- Full text online
- Order with fees

Article ; Online: CCN-Based Therapeutic Peptides Modify Pancreatic Ductal Adenocarcinoma Microenvironment and Decrease Tumor Growth in Combination with Chemotherapy.

Resovi, Andrea / Borsotti, Patrizia / Ceruti, Tommaso / Passoni, Alice / Zucchetti, Massimo / Berndt, Alexander / Riser, Bruce L / Taraboletti, Giulia / Belotti, Dorina

Cells

2020 Volume 9, Issue 4

Abstract: The prominent desmoplastic stroma of pancreatic ductal adenocarcinoma (PDAC) is a determinant factor in tumor progression and a major barrier to the access of chemotherapy. The PDAC microenvironment therefore appears to be a promising therapeutic target. ...

Abstract	The prominent desmoplastic stroma of pancreatic ductal adenocarcinoma (PDAC) is a determinant factor in tumor progression and a major barrier to the access of chemotherapy. The PDAC microenvironment therefore appears to be a promising therapeutic target. CCN2/CTGF is a profibrotic matricellular protein, highly present in the PDAC microenvironment and associated with disease progression. Here we have investigated the therapeutic value of the CCN2-targeting BLR100 and BLR200, two modified synthetic peptides derived from active regions of CCN3, an endogenous inhibitor of CCN2. In a murine orthotopic PDAC model, the two peptides, administered as monotherapy at low doses (approximating physiological levels of CCN3), had tumor inhibitory activity that increased with the dose. The peptides affected the tumor microenvironment, inhibiting fibrosis and vessel formation and reducing necrosis. Both peptides were active in preventing ascites formation. An increased activity was obtained in combination regimens, administering BLR100 or BLR200 with the chemotherapeutic drug gemcitabine. Pharmacokinetic analysis indicated that the improved activity of the combination was not mainly determined by the substantial increase in gemcitabine delivery to tumors, suggesting other effects on the tumor microenvironment. The beneficial remodeling of the tumor stroma supports the potential value of these CCN3-derived peptides for targeting pathways regulated by CCN2 in PDAC.
MeSH term(s)	Adenocarcinoma/drug therapy ; Animals ; Carcinoma, Pancreatic Ductal/drug therapy ; Cell Line, Tumor ; Female ; Humans ; Mice ; Peptides/metabolism ; Tumor Microenvironment
Chemical Substances	Peptides
Language	English
Publishing date	2020-04-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells9040952
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Thrombospondin-1 promotes mesenchymal stromal cell functions via TGFβ and in cooperation with PDGF.

Belotti, Dorina / Capelli, Chiara / Resovi, Andrea / Introna, Martino / Taraboletti, Giulia

Matrix biology : journal of the International Society for Matrix Biology

2016 Volume 55, Page(s) 106–116

Abstract: Mesenchymal stromal cells (MSC) are characterized by unique tropism for wounded tissues, high differentiating capacity, ability to induce tissue repair, and anti-inflammatory and immunoregulatory activities. This has generated interest in their ... ...

Abstract	Mesenchymal stromal cells (MSC) are characterized by unique tropism for wounded tissues, high differentiating capacity, ability to induce tissue repair, and anti-inflammatory and immunoregulatory activities. This has generated interest in their therapeutic use in severe human conditions as well as in regenerative medicine and tissue engineering. Identification of factors involved in the regulation of MSC proliferation, migration and differentiation could provide insights into the pathophysiological regulation of MSC and be exploited to optimize clinical grade expansion protocols for therapeutic use. Here we identify thrombospondin-1 (TSP-1) as a major regulator of MSC. TSP-1 induced MSC proliferation. This effect was mediated by TSP-1-induced activation of endogenous TGFβ, as shown by the inhibitory effects of anti-TGFβ antibodies and by the lack of activity of TSP-2 - that does not activate TGFβ. Moreover, TSP-1 strongly potentiated the proliferative and migratory activity of PDGF on MSC. TSP-1 directly bound to PDGF, through a site located within the TSP-1 type III repeats, and protected the growth factor from degradation by MSC-derived proteases, hence increasing its stability and bioavailability. The studies presented here identify a more comprehensive picture of the pleiotropic effect of TSP-1 on MSC behavior, setting the basis for further studies aimed at investigating the possible use of PDGF and TSP-1 in the in vitro expansion of MSC for therapeutic applications.
Language	English
Publishing date	2016-09
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1183793-7
ISSN	1569-1802 ; 0945-053X
ISSN (online)	1569-1802
ISSN	0945-053X
DOI	10.1016/j.matbio.2016.03.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1694: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito