Chondrocyte hypertrophy and apoptosis induced by GROα require three-dimensional interaction with the extracellular matrix and a co-receptor role of chondroitin sulfate and are associated with the mitochondrial splicing variant of cathepsin B

2006 ◽  
Vol 210 (2) ◽  
pp. 417-427 ◽  
Author(s):  
Eleonora Olivotto ◽  
Roberta Vitellozzi ◽  
Patricia Fernandez ◽  
Elisabetta Falcieri ◽  
Michela Battistelli ◽  
...  
Author(s):  
Lowell Taylor Edgar ◽  
James E. Guilkey ◽  
Clayton J. Underwood ◽  
Brenda Baggett ◽  
Urs Utzinger ◽  
...  

The process of angiogenesis is regulated by both chemical and mechanical signaling. While the role of chemical factors such as vascular endothelial growth factor (VEGF) during angiogenesis has been extensively studied, the influence of the mechanostructural environment on new vessel generation has received significantly less attention. During angiogenesis, endothelial cells in the existing vasculature detach and migrate out into the surrounding extracellular matrix (ECM), forming tubular structures that eventually mature into new blood vessels. This process is modulated by the structure and composition of the ECM [1]. The ECM is then remodeled by endothelial cells in the elongating neovessel tip, resulting in matrix condensation and changes in fiber orientation [2]. The mechanism as to how angiogenic vasculature and the ECM influence each other is poorly understood.


Blood ◽  
2010 ◽  
Vol 115 (7) ◽  
pp. 1444-1452 ◽  
Author(s):  
Céline Cougoule ◽  
Véronique Le Cabec ◽  
Renaud Poincloux ◽  
Talal Al Saati ◽  
Jean-Louis Mège ◽  
...  

Abstract Tissue infiltration of phagocytes exacerbates several human pathologies including chronic inflammations or cancers. However, the mechanisms involved in macrophage migration through interstitial tissues are poorly understood. We investigated the role of Hck, a Src-family kinase involved in the organization of matrix adhesion and degradation structures called podosomes. In Hck−/− mice submitted to peritonitis, we found that macrophages accumulated in interstitial tissues and barely reached the peritoneal cavity. In vitro, 3-dimensional (3D) migration and matrix degradation abilities, 2 protease-dependent properties of bone marrow–derived macrophages (BMDMs), were affected in Hck−/− BMDMs. These macrophages formed few and undersized podosome rosettes and, consequently, had reduced matrix proteolysis operating underneath despite normal expression and activity of matrix metalloproteases. Finally, in fibroblasts unable to infiltrate matrix, ectopic expression of Hck provided the gain–of–3D migration function, which correlated positively with formation of podosome rosettes. In conclusion, spatial organization of podosomes as large rosettes, proteolytic degradation of extracellular matrix, and 3D migration appeared to be functionally linked and regulated by Hck in macrophages. Hck, as the first protein combining a phagocyte-limited expression with a role in 3D migration, could be a target for new anti-inflammatory and antitumor molecules.


2007 ◽  
Vol 82B (1) ◽  
pp. 122-128 ◽  
Author(s):  
Kevin J. Cronin ◽  
Aurora Messina ◽  
Erik W. Thompson ◽  
Wayne A. Morrison ◽  
Geoffrey W. Stevens ◽  
...  

2009 ◽  
Vol 89B (2) ◽  
pp. 575-575
Author(s):  
Kevin J. Cronin ◽  
Aurora Messina ◽  
Erik W. Thompson ◽  
Wayne A. Morrison ◽  
Geoffrey W. Stevens ◽  
...  

2018 ◽  
Vol 40 (1) ◽  
pp. 41-51 ◽  
Author(s):  
Matthew Dean ◽  
Vivian Jin ◽  
Angela Russo ◽  
Daniel D Lantvit ◽  
Joanna E Burdette

Abstract High-grade serous ovarian cancer (HGSOC) can originate in the fallopian tube epithelium (FTE), but the role of the ovary in these tumors is unclear. Tumorigenic murine oviductal epithelial (MOE) cells allografted in the ovarian bursa resulted in aggressive tumors that spread throughout the peritoneum whereas intraperitoneal xenografting the same number of cells did not form tumors, indicating that colonization of the ovary may play a role in metastasis. Physical tearing of the ovarian surface to mimic rupture of the ovary during ovulation (independent of hormonal changes) resulted in more MOE and HGSOC cells adhering to the ovary compared with intact ovaries. More MOE cells also adhered to three-dimensional (3D) collagen and primary ovarian stromal cells than to ovarian surface epithelia, indicating that FTE cells adhered to the extracellular matrix exposed during ovulation. However, plating cells on 3D collagen reduced the viability of normal FTE but not cancer cells. Mutation of p53 (R273H or R248W) and activation of Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) (G12V) did not increase the viability of MOE cells on 3D collagen. In contrast, loss of phosphatase and tensin homolog (PTEN) allowed MOE cells to retain normal viability on 3D collagen. Loss of PTEN activated AKT and RAC1/c-jun N-terminal kinase signaling that each contributed to the increased viability, invasion and attachment in the collagen rich ovarian microenvironment. These results show that loss of PTEN activates multiple pathways that together enhance colonization of the ovary due to access to 3D collagen, which is a critical organ in the colonization of FTE-derived HGSOC.


2008 ◽  
Vol 85B (1) ◽  
pp. 300-300
Author(s):  
Kevin J. Cronin ◽  
Aurora Messina ◽  
Erik W. Thompson ◽  
Wayne A. Morrison ◽  
Geoffrey W. Stevens ◽  
...  

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