8.3 Growth factor signaling and extracellular matrix

Nikitovic, Dragana; Pratsinis, Harris; Berdiaki, Aikaterini; Gialeli, Chrysostomi; Kletsas, Dimitris; Tzanakakis, George N.

doi:10.1515/9783110258776.741

Cited by 4 publications

(6 citation statements)

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“…This may be the result of the lower basal DNA synthesis levels observed in the control 3D cultures, at least regarding AF cells, in agreement with previous observations in other cell types concerning the growth restraining properties of the polymerized collagen [ 19 , 31 ]. On the other hand, the more intense response to growth factors in the 3D environments may simply reflect an increased complexity of the network of activated signaling molecules compared to the monolayer cultures [ 32 ]. In general, the intensity of the proliferative responses to each growth factor in the 3D culture environments follows a similar pattern with that in monolayers, that is, PDGF > IGF-I > bFGF ( Figure 1 ; [ 15 , 16 ]).…”

Section: Discussionmentioning

confidence: 99%

Organotypic Cultures of Intervertebral Disc Cells: Responses to Growth Factors and Signaling Pathways Involved

Pratsinis

Kletsas

2015

BioMed Research International

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Intervertebral disc (IVD) degeneration is strongly associated with low back pain, a major cause of disability worldwide. An in-depth understanding of IVD cell physiology is required for the design of novel regenerative therapies. Accordingly, aim of this work was the study of IVD cell responses to mitogenic growth factors in a three-dimensional (3D) organotypic milieu, comprising characteristic molecules of IVD's extracellular matrix. In particular, annulus fibrosus (AF) cells were cultured inside collagen type-I gels, while nucleus pulposus (NP) cells in chondroitin sulfate A (CSA) supplemented collagen gels, and the effects of Platelet-Derived Growth Factor (PDGF), basic Fibroblast Growth Factor (bFGF), and Insulin-Like Growth Factor-I (IGF-I) were assessed. All three growth factors stimulated DNA synthesis in both AF and NP 3D cell cultures, with potencies similar to those observed previously in monolayers. CSA supplementation inhibited basal DNA synthesis rates, without affecting the response to growth factors. ERK and Akt were found to be phosphorylated following growth factor stimulation. Blockade of these two signaling pathways using pharmacologic inhibitors significantly, though not completely, inhibited growth factor-induced DNA synthesis. The proposed culture systems may prove useful for further in vitro studies aiming at future interventions for IVD regeneration.

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Section: Discussionmentioning

confidence: 99%

Organotypic Cultures of Intervertebral Disc Cells: Responses to Growth Factors and Signaling Pathways Involved

Pratsinis

Kletsas

2015

BioMed Research International

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“…Thus, treatment of cells with PDGF‐BB affected PDGF‐R activation levels. The cellular effects of the PDGF‐R signaling pathway are mainly mediated by the Erk/MAPK and PI3K/Akt signaling cascade . In all breast cancer cell lines tested, both Erk1/2 and Akt were constitutively phosphorylated, while PDGF‐BB treatment resulted in further enhancement of Erk1/2 activation, especially in the highly metastatic MDA‐MB‐231 cells.…”

Section: Discussionmentioning

confidence: 99%

“…Breast carcinomas are known to express PDGF; however, the availability of PDGF-Rs on the target cell is naturally crucial to the PDGFdependent cellular responses and is subject to regulation. For this reason, we evaluated the expression of signaling pathway are mainly mediated by the Erk/ MAPK and PI3K/Akt signaling cascade [13,23,[36][37][38].…”

Section: Discussionmentioning

confidence: 99%

Imatinib as a key inhibitor of the platelet‐derived growth factor receptor mediated expression of cell surface heparan sulfate proteoglycans and functional properties of breast cancer cells

et al. 2013

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Cell surface heparan sulfate proteoglycans (HSPGs), syndecans and glypicans, play crucial roles in the functional properties of cancer cells, such as proliferation, adhesion, migration and invasion. Platelet-derived growth factor (PDGF)/PDGF receptor (PDGF-R) mediated signaling, on the other hand, is highly associated with cancer progression. Specifically, PDGF-Ra and PDGF-Rb expressions documented in breast cancer tissue specimens as well as breast cancer cell lines are correlated with tumor aggressiveness and metastasis. Imatinib (Glivec Ò ) is a tyrosine kinase inhibitor specific for PDGF-Rs, c-ΚΙΤ and BCR-ABL. In this study we evaluated the effects of imatinib on the properties of breast cancer cells as well as on the expression of HSPGs in the presence and absence of PDGF-BB. These studies have been conducted in a panel of three breast cancer cell lines of low and high metastatic potential. Our results indicate that imatinib exerts a significant inhibitory effect on breast cancer cell proliferation, invasion and migration as well as on the cell surface expression of HSPGs even after exposure of PDGF. These effects depend on the aggressiveness of breast cancer cells and the type of HSPG. It is suggested that imatinib may be of potential therapeutic usefulness in breast cancer regimes.

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“…Growth factors have been demonstrated to regulate the production of hyaluronan through the modulation of hyaluronan metabolic enzymes expressions under both pathological and physiological conditions [88]. This is also the case in fibrosarcoma cells, as FGF-2 stimulates in a cell-specific manner the migration capability of fibrosarcoma cells by decreasing HYAL-2 expression in HT1080 cells and by increasing HAS1 and -2 expressions [34].…”

Section: Hyaluronan Expression In Tumor Cells and Its Role In Cancmentioning

confidence: 99%

“…The alterations of ECM components, cell shape, and changes at the cell-ECM interface are considered as important hallmarks of cancer [22–27]. Abnormal ECM also indirectly affects cancer cells by influencing the behaviour of stromal cells, including endothelial cells, immune cells, and fibroblasts, which are the main initial culprits that cause abnormal ECM production [28, 29].…”

Section: Introductionmentioning

confidence: 99%

The Roles of Hyaluronan/RHAMM/CD44 and Their Respective Interactions along the Insidious Pathways of Fibrosarcoma Progression

Nikitovic

Kouvidi

Karamanos

et al. 2013

BioMed Research International

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Fibrosarcomas are rare malignant mesenchymal tumors originating from fibroblasts. Importantly, fibrosarcoma cells were shown to have a high content and turnover of extracellular matrix (ECM) components including hyaluronan (HA), proteoglycans, collagens, fibronectin, and laminin. ECMs are complicated structures that surround and support cells within tissues. During cancer progression, significant changes can be observed in the structural and mechanical properties of the ECM components. Importantly, hyaluronan deposition is usually higher in malignant tumors as compared to benign tissues, predicting tumor progression in some tumor types. Furthermore, activated stromal cells are able to produce tissue structure rich in hyaluronan in order to promote tumor growth. Key biological roles of HA result from its interactions with its specific CD44 and RHAMM (receptor for HA-mediated motility) cell-surface receptors. HA-receptor downstream signaling pathways regulate in turn cellular processes implicated in tumorigenesis. Growth factors, including PDGF-BB, TGFβ2, and FGF-2, enhanced hyaluronan deposition to ECM and modulated HA-receptor expression in fibrosarcoma cells. Indeed, FGF-2 through upregulation of specific HAS isoforms and hyaluronan synthesis regulated secretion and net hyaluronan deposition to the fibrosarcoma pericellular matrix modulating these cells' migration capability. In this paper we discuss the involvement of hyaluronan/RHAMM/CD44 mediated signaling in the insidious pathways of fibrosarcoma progression.

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8.3 Growth factor signaling and extracellular matrix

Cited by 4 publications

References 0 publications

Organotypic Cultures of Intervertebral Disc Cells: Responses to Growth Factors and Signaling Pathways Involved

Organotypic Cultures of Intervertebral Disc Cells: Responses to Growth Factors and Signaling Pathways Involved

Imatinib as a key inhibitor of the platelet‐derived growth factor receptor mediated expression of cell surface heparan sulfate proteoglycans and functional properties of breast cancer cells

The Roles of Hyaluronan/RHAMM/CD44 and Their Respective Interactions along the Insidious Pathways of Fibrosarcoma Progression

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