scholarly journals Lysyl-Oxidase Dependent Extracellular Matrix Stiffness in Hodgkin Lymphomas: Mechanical and Topographical Evidence

Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 259
Author(s):  
Massimo Alfano ◽  
Irene Locatelli ◽  
Cristina D’Arrigo ◽  
Marco Mora ◽  
Giovanni Vozzi ◽  
...  

Purpose: The biochemical composition and architecture of the extracellular matrix (ECM) is known to condition development and invasiveness of neoplasms. To clarify this point, we analyzed ECM stiffness, collagen cross-linking and anisotropy in lymph nodes (LN) of Hodgkin lymphomas (HL), follicular lymphomas (FL) and diffuse large B-cell lymphomas (DLBCL), compared with non-neoplastic LN (LDN). Methods and Results: We found increased elastic (Young’s) modulus in HL and advanced FL (grade 3A) over LDN, FL grade 1–2 and DLBCL. Digital imaging evidenced larger stromal areas in HL, where increased collagen cross-linking was found; in turn, architectural modifications were documented in FL3A by scanning electron microscopy and enhanced anisotropy by polarized light microscopy. Interestingly, HL expressed high levels of lysyl oxidase (LOX), an enzyme responsible for collagen cross-linking. Using gelatin scaffolds fabricated with a low elastic modulus, comparable to that of non-neoplastic tissues, we demonstrated that HL LN-derived mesenchymal stromal cells and HL cells increased the Young’s modulus of the extracellular microenvironment through the expression of LOX. Indeed, LOX inhibition by β-aminopropionitrile prevented the gelatin stiffness increase. Conclusions: These data indicate that different mechanical, topographical and/or architectural modifications of ECM are detectable in human lymphomas and are related to their histotype and grading.

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e88186 ◽  
Author(s):  
Jan Seifert ◽  
Christian M. Hammer ◽  
Johannes Rheinlaender ◽  
Saadettin Sel ◽  
Michael Scholz ◽  
...  

2019 ◽  
Vol 63 (3) ◽  
pp. 349-364 ◽  
Author(s):  
Sylvain D. Vallet ◽  
Sylvie Ricard-Blum

Abstract The lysyl oxidase family comprises five members in mammals, lysyl oxidase (LOX) and four lysyl oxidase like proteins (LOXL1-4). They are copper amine oxidases with a highly conserved catalytic domain, a lysine tyrosylquinone cofactor, and a conserved copper-binding site. They catalyze the first step of the covalent cross-linking of the extracellular matrix (ECM) proteins collagens and elastin, which contribute to ECM stiffness and mechanical properties. The role of LOX and LOXL2 in fibrosis, tumorigenesis, and metastasis, including changes in their expression level and their regulation of cell signaling pathways, have been extensively reviewed, and both enzymes have been identified as therapeutic targets. We review here the molecular features and three-dimensional structure/models of LOX and LOXLs, their role in ECM cross-linking, and the regulation of their cross-linking activity by ECM proteins, proteoglycans, and by inhibitors. We also make an overview of the major ECM cross-links, because they are the ultimate molecular readouts of LOX/LOXL activity in tissues. The recent 3D model of LOX, which recapitulates its known structural and biochemical features, will be useful to decipher the molecular mechanisms of LOX interaction with its various substrates, and to design substrate-specific inhibitors, which are potential antifibrotic and antitumor drugs.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Md Enamul Hoque ◽  
Tan Jie Ye ◽  
Leng Chuan Yong ◽  
KhairulZaman Mohd Dahlan

This research focuses on synthesis and characterization of sago starch-mixed LDPE biodegradable polymer. Firstly, the effect of variation of starch content on mechanical property (elongation at break and Young’s modulus) and biodegradability of the polymer was studied. The LDPE was combined with 10%, 30%, 50%, and 70% of sago for this study. Then how the cross-linking with trimethylolpropane triacrylate (TMPTA) and electron beam (EB) irradiation influence the mechanical and thermal properties of the polymer was investigated. In the 2nd study, to avoid overwhelming of data LDPE polymer was incorporated with only 50% of starch. The starch content had direct influence on mechanical property and biodegradability of the polymer. The elongation at break decreased with increase of starch content, while Young’s modulus and mass loss (i.e., degradation) were found to increase with increase of starch content. Increase of cross-linker (TMPTA) and EB doses also resulted in increased Young’s modulus of the polymer. However, both cross-linking and EB irradiation processes rendered lowering of polymer’s melting temperature. In conclusion, starch content and modification processes play significant roles in controlling mechanical, thermal, and degradation properties of the starch-mixed LDPE synthetic polymer, thus providing the opportunity to modulate the polymer properties for tailored applications.


Hypertension ◽  
2009 ◽  
Vol 53 (2) ◽  
pp. 236-242 ◽  
Author(s):  
Begoña López ◽  
Ramón Querejeta ◽  
Arantxa González ◽  
Javier Beaumont ◽  
Mariano Larman ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Xiangchen Tao ◽  
Haiqun Yu ◽  
Yong Zhang ◽  
Zhiwei Li ◽  
Vishal Jhanji ◽  
...  

Purpose. To evaluate the role of corneal epithelium in riboflavin/ultraviolet-A (UVA) mediated corneal collagen cross-linking treatment.Methods. Fifty New Zealand rabbits were divided into 5 groups: UVA treatment with or without corneal epithelium, UVA+riboflavin treatment with or without corneal epithelium, and control without any treatment. All rabbits were sacrificed after irradiation and subsequently 4 mm × 10 mm corneal strips were harvested for biomechanical evaluation.Results. UVA irradiation alone did not enhance the maximal stress and Young’s modulus of corneal specimens with (3.15 ± 0.56 mpa, 1.00 ± 0.09 mpa) or without (3.53 ± 0.85 mpa, 0.94 ± 0.21 mpa) the corneal epithelium, compared to specimens in the control group (4.30 ± 0.68 mpa, 1.03 ± 0.24 mpa). However, UVA irradiation combined with riboflavin significantly increased the maximal stress and Young’s modulus of corneal specimens with (5.27 ± 1.09 mpa, 1.23 ± 0.23 mpa,P<0.05) or without (7.16 ± 1.88 mpa, 1.42 ± 0.16 mpa,P<0.05) corneal epithelium when compared to the control group. The maximal stress and Young’s modulus of cornea in UVA+riboflavin and “epithelium-off” group were 35.9% and 15.4% higher compared to the UVA+riboflavin and “epithelium-on” group, respectively (P<0.05).Conclusions. Our study shows that UVA+riboflavin treatment significantly affects the biomechanical properties of the cornea with and without epithelial removal. However, corneas without epithelium seem to benefit more compared to corneas with the epithelium.


2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Yali Zhang ◽  
Zhiwei Li ◽  
Lei Liu ◽  
Xuguang Han ◽  
Xiaomin Zhao ◽  
...  

Purpose. To compare the biomechanical properties of porcine, rabbit, and human sclera before and after riboflavin/ultraviolet-A (UVA) collagen cross-linking (CXL).Methods. Eight rabbits, 8 porcine eyeballs, and 8 human eyeballs were included. One rabbit eye and half of each bisected human and porcine eyeball were treated with riboflavin/UVA CXL. Untreated fellow rabbit eyes and eyeball halves served as controls. A 10 mm × 20 mm scleral band was harvested from each specimen. From this band, two 3.5 mm × 15.0 mm strips were prepared for biomechanical testing. The biomechanical parameters were ultimate stress, stress and Young’s modulus.Results. Values of stress, and Young’s modulus showed that human sclera was 4 times stiffer than porcine sclera and 3 times stiffer than rabbit sclera. In rabbit sclera, both the stress and Young’s modulus were significantly increased by CXL (P<0.05). In porcine sclera, only the ultimate stress was significantly increased by CXL (P<0.05). The biomechanical properties of human sclera were not statistically affected by CXL (P>0.05).Conclusions. Human sclera has higher biomechanical stiffness than porcine and rabbit sclera. With the same irradiation dose, riboflavin/UVA CXL increases the biomechanical stiffness of rabbit sclera but not porcine or human sclera.


2004 ◽  
Vol 851 ◽  
Author(s):  
S. J. V. Frankland ◽  
M. N. Herzog ◽  
G. M. Odegard ◽  
T. S. Gates ◽  
C. C. Fay

ABSTRACTSynthesis, mechanical testing, and modeling have been performed for a carbon nanotube material in which the nanotubes are functionalized with variable stiffness tethers (VST) capable of cross-linking the nanotubes. Tests using nanoindentation indicated a six-fold enhancement in the storage modulus when comparing the base material (the cross-linking agent with no nanotubes) to the composite (functionalized nanotube material) that contained 5.3 wt% of nanotubes. To understand how crosslinking the nanotubes may further alter the stiffness, a model of the system was constructed using nanotubes crosslinked with the VST. The model predicted that for a composite with 5 wt% nanotubes at random orientations, crosslinked with the VST, the bulk Young's modulus was reduced to 30% that of the non-crosslinked equivalent.


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