The Experts below are selected from a list of 153 Experts worldwide ranked by ideXlab platform
Susanne Grässel - One of the best experts on this subject based on the ideXlab platform.
-
The NC11 domain of human Collagen XVI induces vasculogenic mimicry in oral squamous cell carcinoma cells
Carcinogenesis, 2015Co-Authors: Konstanze B. Bedal, Susanne Grässel, Gerrit Spanier, Torsten E. Reichert, Richard BauerAbstract:Collagen XVI, a fibril-associated Collagen with interrupted triple helix (FACIT) Collagen, is involved in oral squamous cell carcinoma (OSCC) and glioblastoma progression. The NC11 domain of Collagen XVI has been described previously with a strong implication in physiological processes. We detected the non-Collagenous (NC) 11-domain in supernatants of OSCC cells after recombinant expression of full-length Collagen XVI and in sera from OSCC patients and healthy individuals. Stable expression of NC11-green fluorescent protein (GFP) fusion protein in OSCC cells initiated proliferation control and block of anchorage-independent growth. Moreover, the NC11 domain triggered the generation of tubular-like net structures on laminin-rich matrix in contrast to mock-GFP control cells and cells expressing full-length Collagen XVI. Taqman® quantitative PCR and diaminobenzidine staining in 2D- and 3D cell culture revealed a significantly increased gene and protein expression of VEGFR1, VEGFR2 and uPAR in recombinant NC11-GFP-expressing cells. Specific VEGF receptor inhibition with Axitinib or fetal calf serum heat inactivation prevented formation of tubular-like net structures. Accordantly, NC11-GFP coated culture slides led to an increase of focal adhesion contact formation and the upregulation of VEGFR1 and uPAR in three different non-transfected OSCC cell lines. In summary, we suggest that the NC11 domain of Collagen XVI is a potential biomarker for OSCC and triggers vasculogenic mimicry via upregulation of endothelial receptors VEGFR1, VEGFR2 and uPAR in 2D- and 3D OSCC cell culture conditions.
-
Collagen XVI expression is upregulated in glioblastomas and promotes tumor cell adhesion
FEBS Letters, 2008Co-Authors: Volker Senner, Sabine Ratzinger, Sonja Mertsch, Susanne Grässel, Werner PaulusAbstract:The poor prognosis of glioblastoma patients is related to diffuse brain invasion and interaction of tumor cells with extracellular matrices (ECM). We describe expression and function of the FACIT-Collagen XVI in glioblastomas. We found upregulation of Collagen XVI mRNA as well as protein in glioblastomas as compared to normal cortex. SiRNA knockdown resulted in decreased cell adhesion whereas increased adhesion was observed on surfaces coated with Collagen XVI. The migration of glioblastoma cells on this substrate remained unchanged. Our results demonstrate de-novo expression of Collagen XVI in glioblastomas as part of the tumor specific remodeling of the ECM.
-
Molecular Structure and Interaction of Recombinant Human Type XVI Collagen
Journal of molecular biology, 2004Co-Authors: Anja Kassner, Kerstin Tiedemann, Holger Notbohm, Thomas Ludwig, Matthias Mörgelin, Dieter P. Reinhardt, Mon-li Chu, Peter Bruckner, Susanne GrässelAbstract:Collagen XVI is a minor component of at least two different extracellular fibrillar networks of specialized regions of skin and cartilage. In skin, Collagen XVI is integrated into particular fibrillin-rich microfibrils lacking an amorphous elastin core. In cartilage, Collagen XVI is a component of small heterotypic D-banded fibrils, mainly occurring in the territorial matrix of chondrocytes. Here, we present the first direct evidence for the molecular structure and functional properties of these fibril-associated Collagens with interrupted triple helices (FACIT). We have expressed recombinantly the full-length alpha1 chain of human Collagen XVI in HEK 293 EBNA cells in large quantities using an episomal expression system. Secreted full-length recombinant Collagen XVI forms stable disulfide-bonded homotrimers and is rapidly proteolytically processed to distinct fragments at specific protease sequence motifs, one resembling an aggrecanase recognition site. Limited trypsin digestion assays and thermal transition curves imply sequential thermal denaturation of individual triple helical domains of this recombinant Collagen, similar to authentic Collagen XVI. Molecular images of Collagen XVI reveal rod-like molecules which harbor multiple sharp kinks attributing a highly flexible structure presumably introduced by non-Collagenous (NC) regions. Terminally located cloverleaf-shaped nodules correspond to the large NC NC11 domain of trimeric Collagen XVI. The total length of individual trimeric recombinant Collagen XVI molecules constitutes about 240 nm as calculated by atomic force and negative staining electron microscopy. Recombinant Collagen XVI interacts with fibrillin-1 and with fibronectin indicating multiple molecular interactions in which this ubiquitously expressed and versatile FACIT-Collagen can participate. In vitro generated Collagen XVI provides an indispensable tool for future determination of its function during supramolecular assembly of matrix aggregates and its role in maintenance, organization and interaction of fibrillar structures. (C) 2004 Elsevier Ltd. All rights reserved. (Less)
Nicolò Parrinello - One of the best experts on this subject based on the ideXlab platform.
-
FACIT Collagen (1α-chain) is expressed by hemocytes and epidermis during the inflammatory response of the ascidian Ciona intestinalis
Developmental and comparative immunology, 2007Co-Authors: Aiti Vizzini, Margherita Pergolizzi, Mirella Vazzana, Giuseppina Salerno, Caterina Di Sano, Pasquale Macaluso, Vincenzo Arizza, Daniela Parrinello, Matteo Cammarata, Nicolò ParrinelloAbstract:Summary Based on previous cloning and sequencing study, real-time PCR and in situ hybridization assays of the inflamed body wall of LPS-injected Ciona intestinalis showed the enhanced gene expression of a Collagen with FACIT structural features ( Ci -type IX-Col 1 α -chain). By using specific antibodies raised against an opportunely chosen Ci -type IX-Col synthetic peptide, the fibroblast property of hemocytes challenged in vitro with LPS (at 4 h) was displayed by flow cytometry, while immunocytochemistry identified hemocytes with large granules (morula cells) as Collagen-producing cells. Hemocyte lysate supernatant analyzed in immunoblotting contained a 60 kDa band identifiable as 1 α -chain- Ci -type IX-Col. Observations of body wall sections (immunohistochemistry method) supported the role of hemocytes and showed that epidermis expressed Ci -type IX-Col 1 α -chain in the time course of the inflammatory reaction (within 24 h). Transcript and protein were mainly found in the epidermis that outlined the proximal side of the tunic matrix (at 24 h after LPS injection), in cells associated with the epidermis at 4 and 192 h. In conclusion, the C. intestinalis inflammatory response to LPS challenge appeared to be composed of a complex reaction set, and for the first time we showed in ascidians a granulation tissue with FACIT-Collagen production that could participate in inflammation and wound healing. Like in vertebrates, C. intestinalis acute inflammatory reactions result in a regulated pattern of tissue repair with Collagen expression during remodelling. Ci -type IX-Col could be involved in a network of non-fibril-forming Collagens that participates in the organization of extracellular matrix and defense responses.
Werner Paulus - One of the best experts on this subject based on the ideXlab platform.
-
Collagen XVI expression is upregulated in glioblastomas and promotes tumor cell adhesion
FEBS Letters, 2008Co-Authors: Volker Senner, Sabine Ratzinger, Sonja Mertsch, Susanne Grässel, Werner PaulusAbstract:The poor prognosis of glioblastoma patients is related to diffuse brain invasion and interaction of tumor cells with extracellular matrices (ECM). We describe expression and function of the FACIT-Collagen XVI in glioblastomas. We found upregulation of Collagen XVI mRNA as well as protein in glioblastomas as compared to normal cortex. SiRNA knockdown resulted in decreased cell adhesion whereas increased adhesion was observed on surfaces coated with Collagen XVI. The migration of glioblastoma cells on this substrate remained unchanged. Our results demonstrate de-novo expression of Collagen XVI in glioblastomas as part of the tumor specific remodeling of the ECM.
Aiti Vizzini - One of the best experts on this subject based on the ideXlab platform.
-
FACIT Collagen (1α-chain) is expressed by hemocytes and epidermis during the inflammatory response of the ascidian Ciona intestinalis
Developmental and comparative immunology, 2007Co-Authors: Aiti Vizzini, Margherita Pergolizzi, Mirella Vazzana, Giuseppina Salerno, Caterina Di Sano, Pasquale Macaluso, Vincenzo Arizza, Daniela Parrinello, Matteo Cammarata, Nicolò ParrinelloAbstract:Summary Based on previous cloning and sequencing study, real-time PCR and in situ hybridization assays of the inflamed body wall of LPS-injected Ciona intestinalis showed the enhanced gene expression of a Collagen with FACIT structural features ( Ci -type IX-Col 1 α -chain). By using specific antibodies raised against an opportunely chosen Ci -type IX-Col synthetic peptide, the fibroblast property of hemocytes challenged in vitro with LPS (at 4 h) was displayed by flow cytometry, while immunocytochemistry identified hemocytes with large granules (morula cells) as Collagen-producing cells. Hemocyte lysate supernatant analyzed in immunoblotting contained a 60 kDa band identifiable as 1 α -chain- Ci -type IX-Col. Observations of body wall sections (immunohistochemistry method) supported the role of hemocytes and showed that epidermis expressed Ci -type IX-Col 1 α -chain in the time course of the inflammatory reaction (within 24 h). Transcript and protein were mainly found in the epidermis that outlined the proximal side of the tunic matrix (at 24 h after LPS injection), in cells associated with the epidermis at 4 and 192 h. In conclusion, the C. intestinalis inflammatory response to LPS challenge appeared to be composed of a complex reaction set, and for the first time we showed in ascidians a granulation tissue with FACIT-Collagen production that could participate in inflammation and wound healing. Like in vertebrates, C. intestinalis acute inflammatory reactions result in a regulated pattern of tissue repair with Collagen expression during remodelling. Ci -type IX-Col could be involved in a network of non-fibril-forming Collagens that participates in the organization of extracellular matrix and defense responses.
Anja Kassner - One of the best experts on this subject based on the ideXlab platform.
-
Molecular Structure and Interaction of Recombinant Human Type XVI Collagen
Journal of molecular biology, 2004Co-Authors: Anja Kassner, Kerstin Tiedemann, Holger Notbohm, Thomas Ludwig, Matthias Mörgelin, Dieter P. Reinhardt, Mon-li Chu, Peter Bruckner, Susanne GrässelAbstract:Collagen XVI is a minor component of at least two different extracellular fibrillar networks of specialized regions of skin and cartilage. In skin, Collagen XVI is integrated into particular fibrillin-rich microfibrils lacking an amorphous elastin core. In cartilage, Collagen XVI is a component of small heterotypic D-banded fibrils, mainly occurring in the territorial matrix of chondrocytes. Here, we present the first direct evidence for the molecular structure and functional properties of these fibril-associated Collagens with interrupted triple helices (FACIT). We have expressed recombinantly the full-length alpha1 chain of human Collagen XVI in HEK 293 EBNA cells in large quantities using an episomal expression system. Secreted full-length recombinant Collagen XVI forms stable disulfide-bonded homotrimers and is rapidly proteolytically processed to distinct fragments at specific protease sequence motifs, one resembling an aggrecanase recognition site. Limited trypsin digestion assays and thermal transition curves imply sequential thermal denaturation of individual triple helical domains of this recombinant Collagen, similar to authentic Collagen XVI. Molecular images of Collagen XVI reveal rod-like molecules which harbor multiple sharp kinks attributing a highly flexible structure presumably introduced by non-Collagenous (NC) regions. Terminally located cloverleaf-shaped nodules correspond to the large NC NC11 domain of trimeric Collagen XVI. The total length of individual trimeric recombinant Collagen XVI molecules constitutes about 240 nm as calculated by atomic force and negative staining electron microscopy. Recombinant Collagen XVI interacts with fibrillin-1 and with fibronectin indicating multiple molecular interactions in which this ubiquitously expressed and versatile FACIT-Collagen can participate. In vitro generated Collagen XVI provides an indispensable tool for future determination of its function during supramolecular assembly of matrix aggregates and its role in maintenance, organization and interaction of fibrillar structures. (C) 2004 Elsevier Ltd. All rights reserved. (Less)
