Endothelial podosome rosettes regulate vascular branching in tumour angiogenesis

Seano, Giorgio; Chiaverina, Giulia; Gagliardi, Paolo Armando; Blasio, Laura di; Puliafito, Alberto; Bouvard, Claire; Sessa, Roberto; Tarone, Guido; Sorokin, Lydia; Helley, Dominique; Jain, Rakesh K.; Serini, Guido; Bussolino, Federico; Primo, Luca

doi:10.1038/ncb3036

Cited by 109 publications

(127 citation statements)

References 44 publications

(73 reference statements)

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“…Most studies have been performed with human umbilical vein endothelial cells (HUVECs) (Osiak et al, 2005) exposed to phorbol esters (Guegan et al, 2008;Seano et al, 2014;Tatin et al, 2006) or with aortic endothelial cells exposed to TGFβ (Curado et al, 2014;Varon et al, 2006). In these situations, podosomes arise in clusters or ring-shaped superstructures that are often called rosettes.…”

Section: Introductionmentioning

confidence: 99%

VEGF-A stimulates podosome-mediated collagen-IV proteolysis in microvascular endothelial cells

Daubon

Spuul

Alonso

et al. 2016

Journal of Cell Science

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Podosomes are dynamic cell-matrix contact structures that combine several key abilities, including adhesion, matrix degradation and mechanosensing. These actin-based cytoskeletal structures are well known in monocytic cells, but much less is known about those formed in other lineages. In this study, we characterize podosomes in capillary-derived microvascular endothelial cells. We identify two types of podosomes: constitutive podosomes that form in the absence of specific stimulation and induced podosomes that arise in response to the angiogenic factor VEGF-A. Constitutive and VEGF-A-induced podosomes share similar components but exhibit marked differences in terms of gelatinolytic activity. We also show that extracellular matrix proteins are key determinants of the VEGF-A response: laminin and collagen-IV, but neither collagen-I nor fibronectin are conducive for podosome induction. Moreover, only collagen-IV elicits the formation of proteolytically active podosomes through a mechanism involving increased Src phosphorylation, p190RhoGAP-B relocalisation and MT1-MMP cell surface exposure at podosome sites. We hypothesise that by promoting podosome formation, VEGF-A enables endothelial cells to overcome the basement membrane barrier for sprouting away from the existing vasculature.

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Section: Introductionmentioning

confidence: 99%

VEGF-A stimulates podosome-mediated collagen-IV proteolysis in microvascular endothelial cells

Daubon

Spuul

Alonso

et al. 2016

Journal of Cell Science

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“…This included 2 VEGF-dependent mouse models of tumor angiogenesis, a mouse model of hind-limb ischemia, and clinical biopsies from human lung tumors. 10 Based on these findings, we proposed the hypothesis that podosome rosettes were specifically expressed by angiogenic endothelium, and we found this to be true in a mouse model of pancreatic insulinoma. The appearance of podosome rosettes increased during tumor progression from the hyperplastic to the malignant stage, and the peak coincided with the VEGF-driven angiogenic switch.…”

Section: Podosome Rosettes and Sprouting Angiogenesismentioning

confidence: 88%

“…More recently, we also noticed the existence of endothelial rosettes in VEGF-stimulated aortic explants. This prompted us to study other VEGF-stimulated vessels, 10 and we were able to detect podosome rosettes in sprouting vessels in adult angiogenic tissues in vivo. This included 2 VEGF-dependent mouse models of tumor angiogenesis, a mouse model of hind-limb ischemia, and clinical biopsies from human lung tumors.…”

Section: Podosome Rosettes and Sprouting Angiogenesismentioning

confidence: 99%

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Podosomes and invadopodia: tools to breach vascular basement membrane

Seano

Primo

2015

Cell Cycle

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T he vascular basement membrane (BM) is a thin and dense crosslinked extracellular matrix layer that covers and protects blood vessels. Understanding how cells cross the physical barrier of the vascular BM will provide greater insight into the potentially critical role of vascular BM breaching in cancer extravasation, leukocyte trafficking and angiogenic sprouting. In the last year, new evidence has mechanistically linked the breaching of vascular BM with the formation of specific cellular microdomains known as podosomes and invadopodia. These structures are specialized cell-matrix contacts with an inherent ability to degrade the extracellular matrix. Specifically, the formation of podosomes or invadopodia was shown as an important step in vascular sprouting and tumor cell extravasation, respectively. Here, we review and comment on these recent findings and explore the functions of podosomes and invadopodia within the context of pathological processes such as tumor dissemination and tumor angiogenesis.

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“…An example is shown in Figure 5I-L, where IQGAP1 + cells are observed in the tunica intima and in tight contact with the tunica adventitia. Endothelial cells lead angiogenesis by developing endothelial podosome/invadopodia rosettes [45], critical in GBM progression. IQGAP1 in podosome/invadopodia.…”

Section: Iqgap1 In Gbm Astrocytes and Gscsmentioning

confidence: 99%

IQGAP1 in Podosome /Invadosome is Involved in the Progression of Glioblastoma Multiforme Depending on the Tumor Status

Rotoli¹,

Pérez-Rodríguez²,

Morales³

et al. 2017

Preprint

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Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor. GBM is formed by a very heterogeneous astrocyte population, neurons, neovascularization and infiltrating myeloid cells (microglia and monocyte derived macrophages). The IQGAP1 scaffold protein interacts with components of the cytoskeleton, cell adhesion molecules, and several signalling molecules to regulate cell morphology and motility, cell cycle and other cellular functions. IQGAP1 overexpression and delocalization has been observed in several tumours, suggesting a role for this protein in cell proliferation, transformation and invasion. IQGAP1 has been identified as a marker of amplifying cancer cells in GBMs. To determine the involvement of IQGAP1 in the onco-biology of GBM, we performed immunohistochemical confocal microscopical analysis of the IQGAP1 protein in human GBM tissue samples using cell type-specific markers. IQGAP1 immunostaining and subcellular localization was heterogeneous; the protein was located in the plasma membrane and, at variable levels, in nucleus and/or cytosol. Moreover, IQGAP1 positive staining was found in podosome/invadopodia-like structures. IQGAP1 + staining was observed in neurons (Map2 + cells), in cancer stem cells (CSC; nestin + ) and in several macrophages (CD31 + or Iba1 + ). Our results indicate that the IQGAP1 protein is involved in normal cell physiology and also in oncologic processes.

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Endothelial podosome rosettes regulate vascular branching in tumour angiogenesis

Cited by 109 publications

References 44 publications

VEGF-A stimulates podosome-mediated collagen-IV proteolysis in microvascular endothelial cells

VEGF-A stimulates podosome-mediated collagen-IV proteolysis in microvascular endothelial cells

Podosomes and invadopodia: tools to breach vascular basement membrane

IQGAP1 in Podosome /Invadosome is Involved in the Progression of Glioblastoma Multiforme Depending on the Tumor Status

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