Tenascin-C in the extracellular matrix promotes the selection of highly proliferative and tubulogenesis-defective endothelial cells

Alves, Tércia; Fonseca, Anna Carolina Carvalho da; Nunes, Sara S.; Silva, Aline Oliveira da; Dubois, Luiz Gustavo; Faria, Jane; Kahn, Suzana Assad; Viana, Nathan B.; Marcondes, Jorge; Legrand, Chantal; Moura‐Neto, Vivaldo; Morandi, Verônica

doi:10.1016/j.yexcr.2011.06.006

Cited by 23 publications

(23 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Freshly immobilized ECMs from astrocytes were obtained as previously described. 31 Briefly, astrocytes in confluent monolayers were disrupted with cold lysis buffer (PBS-Ca 2+ , pH 7.4, containing 0.1% Triton X-100, 0.1 M NH 4 OH, 40 μ M leupeptine and 1 m M PMSF) and cellular debris was washed twice with cold PBS-Ca 2+ .…”

Section: Resultsmentioning

confidence: 99%

“…( a ) Representative photomicrographs of three independent experiments of TUNEL (Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) assay (red, upper panels) and immunofluorescence staining of Ki67 (green, lower panels) of U87MG cells cultured on p53 +/+ or p53 +/− astrocytic ECM for 24 h. Freshly immobilized ECMs from astrocytes were obtained as previously described. 31 TUNEL assay was performed as described by Borges and co-workers. 47 Ki-67 antibody used was purchased from BD Pharmingen, San Diego, CA, USA.…”

Section: Figurementioning

confidence: 99%

See 1 more Smart Citation

Glioblastoma cells inhibit astrocytic p53-expression favoring cancer malignancy

et al. 2014

View full text Add to dashboard Cite

The tumor microenvironment has a dynamic and usually cancer-promoting function during all tumorigenic steps. Glioblastoma (GBM) is a fatal tumor of the central nervous system, in which a substantial number of non-tumoral infiltrated cells can be found. Astrocytes neighboring these tumor cells have a particular reactive phenotype and can enhance GBM malignancy by inducing aberrant cell proliferation and invasion. The tumor suppressor p53 has a potential non-cell autonomous function by modulating the expression of secreted proteins that influence neighbor cells. In this work, we investigated the role of p53 on the crosstalk between GBM cells and astrocytes. We show that extracellular matrix (ECM) from p53+/− astrocytes is richer in laminin and fibronectin, compared with ECM from p53+/+ astrocytes. In addition, ECM from p53+/− astrocytes increases the survival and the expression of mesenchymal markers in GBM cells, which suggests haploinsufficient phenotype of the p53+/– microenvironment. Importantly, conditioned medium from GBM cells blocks the expression of p53 in p53+/+ astrocytes, even when DNA was damaged. These results suggest that GBM cells create a dysfunctional microenvironment based on the impairment of p53 expression that in turns exacerbates tumor endurance.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Glioblastoma cells inhibit astrocytic p53-expression favoring cancer malignancy

et al. 2014

View full text Add to dashboard Cite

show abstract

“…From the mass spectrometry analysis, we identified Tenascin-C in the tECM but not nECM. It is known to be abundant in tumor tissues and to have an important role in endothelial proliferation and vessel malformations [54]. ECM proteins can bind to several growth factors, making them available to cells during matrix proteolysis, and these factors can stimulate enhanced vasculogenesis and angiogenesis [55].…”

Section: Discussionmentioning

confidence: 99%

Recapitulating the human tumor microenvironment: Colon tumor-derived extracellular matrix promotes angiogenesis and tumor cell growth

et al. 2017

View full text Add to dashboard Cite

Extracellular matrix (ECM) is an essential and dynamic component of all tissues and directly affects cellular behavior by providing both mechanical and biochemical signaling cues. Changes in ECM can alter tissue homeostasis, potentially leading to promotion of cellular transformation and the generation of tumors. Therefore, understanding ECM compositional changes during cancer progression is vital to the development of targeted treatments. Previous efforts to reproduce the native 3D cellular microenvironment have utilized protein gels and scaffolds that incompletely recapitulate the complexity of native tissues. Here, we address this problem by extracting and comparing ECM from normal human colon and colon tumor that had metastasized to liver. We found differences in protein composition and stiffness, and observed significant differences in vascular network formation and tumor growth in each of the reconstituted matrices, both in vitro and in vivo. We studied free/bound ratios of NADH in the tumor and endothelial cells using Fluorescence Lifetime Imaging Microscopy as a surrogate for the metabolic state of the cells. We observed that cells seeded in tumor ECM had higher relative levels of free NADH, consistent with a higher glycolytic rate, than those seeded in normal ECM. These results demonstrate that the ECM plays an important role in the growth of cancer cells and their associated vasculature.

show abstract

“…Tenascin C, another ECM element, is directly involved with neovascularization and impairs tubulogenesis of vessels. This ECM protein is present on the surface of GBM and could act on vessels (Alves et al 2011).…”

Section: Characteristics Of Malignant Transformationmentioning

confidence: 99%

“…First, the tumor mass detaches from the original location, involving downregulation of neural cell adhesion molecules (NCAMs) and E-cadherin, as well as upregulation of cell surface glycoprotein (CD44), which functions as an adhesion molecule (Thomas and Speight 2001). The second process is the interaction with the extracellular matrix (ECM), mediated by integrins and tenascin-C (Alves et al 2011;Bellail et al 2004), leading to the degradation and remodeling of the ECM, including the modulation of the metalloproteinase (MMP) activity. These proteases are responsible for the breakdown of the basal membrane, creating and maintaining a microenvironment that facilitates tumor cell survival .…”

Section: The High Invasiveness Of Gliomas: New Molecular Targetsmentioning

confidence: 99%