Multilayer platform to model the bioactivity of hyaluronic acid in gastric cancer

被引:11
作者
Amorim, Sara [1 ,2 ]
da Costa, Diana Soares [1 ,2 ]
Mereiter, Stefan [3 ,4 ]
Pashkuleva, Iva [1 ,2 ]
Reis, Celso A. [3 ,4 ,5 ,6 ]
Reis, Rui L. [1 ,2 ]
Pires, Ricardo A. [1 ,2 ]
机构
[1] Univ Minho, Headquarters European Inst Excellence Tissue Engn, I3Bs Res Inst Biomat Biodegradables & Biomimet, 3Bs Res Grp, AvePk,Parque Ciencia & Tecnol, P-4805017 Barco, Guimaraes, Portugal
[2] ICVS 3Bs PT Govt Associate Lab, Braga, Guimaraes, Portugal
[3] Univ Porto, Inst Invest & Inovacao Saude i3S, Porto, Portugal
[4] Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, Porto, Portugal
[5] Univ Porto, Fac Med, Dept Pathol & Oncol, Porto, Portugal
[6] Univ Porto, Inst Biomed Sci Abel Salazar, Porto, Portugal
来源
MATERIALS SCIENCE AND ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS | 2021年 / 119卷
基金
欧盟地平线“2020”;
关键词
Hyaluronic acid; QCM-D; Cancer invasiveness; Molecular weights; ECM model; ADHESION; PAXILLIN; CELLS; PROGRESSION; FILMS; CD44; GLYCOSAMINOGLYCANS; FILOPODIA; KINASE;
D O I
10.1016/j.msec.2020.111616
中图分类号
TB3 [工程材料学]; R318.08 [生物材料学];
学科分类号
0805 ; 080501 ; 080502 ;
摘要
Hyaluronic acid (HA) has a key role in cancer progression. The HA's molecular weight (M-w) is altered in this pathological state: increased concentration of shorter fragments due to the overexpressed hyaluronidases and ROS. Aiming to mimic this microenvironment, we developed a Layer-by-Layer (LbL) platform presenting HA of different M(w)s, namely 6.4, 752 and 1500 kDa, to study the influence of HA M-w on the formation of focal adhesion sites (FAs), and the involvement of paxillin and CD44 in this process. High paxillin expression and formation of FAs, via CD44, is observed for MKN45 cells seeded on LbLs presenting HA 6.4 kDa, with the activation of the ERK1/2 pathway, responsible for cell motility and tumour progression. In contrast, activation of p38 pathway, usually related with cancer latency, is observed for cells seeded on LbLs with high M-w HA, i.e. 1500 kDa. Overall, we demonstrate the suitability of the developed platform to study cancer invasiveness.
引用
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页数:10
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