Regulation of invadopodia by the tumor microenvironment

Gould, Christine M.; Courtneidge, Sara A.

doi:10.4161/cam.28346

Cited by 70 publications

(59 citation statements)

References 116 publications

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“…Some of the morphological and molecular characteristics of invadopodia are as follows: (i) an actin‐rich core surrounded by a ring of actin‐associated and signaling proteins; (ii) a ventral cell surface, which is often situated under the nucleus; (iii) a length >2 μm; (iv) branched actin filaments at the cell surface and unbranched actin filaments through the tip of the protrusion; (v) pericellular proteolysis via the action of MMP2, MMP9, MT1MMP, seprase/FAP uPAR and some ADAMs; and (vi) a long‐term duration of the structure (on a scale of hours). It is beyond the scope of this review to discuss the molecular aspects of invadopodia and their formation in detail; for more information, please see Murphy and Courtneidge () and Gould and Courtneidge ().…”

Section: Malignant Alterations Of Glioma Cells Increase Their Invasionmentioning

confidence: 99%

Glioma infiltration and extracellular matrix: key players and modulators

Ferrer

Moura‐Neto

Mentlein

2018

Glia

155

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An outstanding characteristic of gliomas is their infiltration into brain parenchyma, a property that impairs complete surgical resection; consequently, these tumors might recur, resulting in a high mortality rate. Gliomas invade along preferential routes, such as those along white matter tracts and in the perineuronal and perivascular spaces. Brain extracellular components and their partners and modulators play a crucial role in glioma cell invasion. This review presents an extensive survey of the literature, showing how the brain extracellular matrix (ECM) is modulated during the glioma infiltration process. We explore aspects of ECM interaction with glioma cells, reviewing the main glycosaminoglycans, glycoproteins and proteoglycans. We discuss the roles of ECM-binding proteins, including CD44, RHAMM, integrins and axonal guidance molecules, and highlight the role of proteases and glycosidases in glioma infiltration; in binding and release chemokines, cytokines and growth factors; and in generating new bioactive ECM fragments. We also consider the roles of cytoskeletal signaling, angiogenesis, miRNAs and the glial-to-mesenchymal transition linked to glioma invasion. We closely discuss therapeutic approaches based on the modulation of the extracellular matrix, targeting the control of glioma infiltration, its relative failure in clinical trials, and potential means to overcome this difficulty.

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Section: Malignant Alterations Of Glioma Cells Increase Their Invasionmentioning

confidence: 99%

Glioma infiltration and extracellular matrix: key players and modulators

Ferrer

Moura‐Neto

Mentlein

2018

Glia

155

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“…Invadosomes are normally associated with tumor cell motility, as a molecular mechanism co-opted and deregulated from normal cells [26,27]. Invadopodia can nonetheless be distinguished due to their overall morphology.…”

Section: Introductionmentioning

confidence: 99%

Polyethylenimine-coated SPION exhibits potential intrinsic anti-metastatic properties inhibiting migration and invasion of pancreatic tumor cells

Mulens-Arias

Rojas

Pérez-Yagüe

et al. 2015

Journal of Controlled Release

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“…In addition to growth factors, a number of signals present in the tumor microenvironment, such as hypoxia, pH or direct interactions with stromal cells were shown to be associated with invasion and metastasis of cancer cells (Gould and Courtneidge, 2014). The production of the pro-inflammatory lipid Prostaglandin E 2 (PGE 2 ) is elevated in breast cancer due to high expression of the prostaglandin-endoperoxidase synthase 2 (COX2), which is a critical determinant for invasiveness of human breast cancer cells (Bocca et al, 2014; Miglietta et al, 2010; Park et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

EP4 receptor promotes invadopodia and invasion in human breast cancer

Tönisen

Perrin

Bayarmagnai

et al. 2017

European Journal of Cell Biology

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The production of Prostaglandin E2 (PGE2) is elevated in human breast cancer cells. The abnormal expression of COX-2, which is involved in the synthesis of PGE2, was recently reported as a critical determinant for invasiveness of human breast cancer cells. Autocrine and paracrine PGE2-mediated stimulation of the PGE2 receptor EP4 transduces multiple signaling pathways leading to diverse patho-physiological effects, including tumor cell invasion and metastasis. It is known that PGE2-induced EP4 activation can transactivate the intracellular signaling pathway of the epidermal growth factor receptor (EGFR). In malignant cancer cells, EGFR pathway activation promotes invadopodia protrusions, which further leads to degradation of the surrounding extracellular matrix (ECM). Despite the known influence of EP4 on the EGFR signaling pathway, the effect of EP4 stimulation on invadopodia formation in human breast cancer was never tested directly. Here we demonstrate the involvement of EP4 in invasion and its effect on invadopodia in breast cancer MDA-MB-231 cells using 2D invadopodia and 3D invasion in vitro assays as well as intravital microscopy. The results show that stimulation with the selective EP4 agonist CAY10598 or PGE2 promotes invadopodia-mediated degradation of the ECM, as well as the invasion of breast cancer cells in in vitro models. The effect on matrix degradation can be abrogated via direct inhibition of EP4 signaling as well as via inhibition of EGFR tyrosine kinase, indicating that EP4-mediated effects on invadopodia-driven degradation are EGFR dependent. Finally, using xenograft mouse models, we show that short-term systemic treatment with CAY10598 results in a >9-fold increase in the number of invadopodia. These findings highlight the importance of further investigation on the role of EP4-EGFR crosstalk in invadopodia formation.

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Regulation of invadopodia by the tumor microenvironment

Cited by 70 publications

References 116 publications

Glioma infiltration and extracellular matrix: key players and modulators

Glioma infiltration and extracellular matrix: key players and modulators

Polyethylenimine-coated SPION exhibits potential intrinsic anti-metastatic properties inhibiting migration and invasion of pancreatic tumor cells

EP4 receptor promotes invadopodia and invasion in human breast cancer

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