TY - JOUR
T1 - Multilayer platform to model the bioactivity of hyaluronic acid in gastric cancer
AU - Amorim, Sara
AU - Costa, Diana Soares da
AU - Mereiter, Stefan
AU - Pashkuleva, Iva
AU - Reis, Celso A.
AU - Reis, Rui L.
AU - Pires, Ricardo A.
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2021/2
Y1 - 2021/2
N2 - Hyaluronic acid (HA) has a key role in cancer progression. The HA's molecular weight (Mw ) 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 ws, 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.
AB - Hyaluronic acid (HA) has a key role in cancer progression. The HA's molecular weight (Mw ) 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 ws, 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.
KW - Hyaluronic acid
KW - QCM-D
KW - Cancer invasiveness
KW - Molecular weights
KW - ECM model
UR - http://www.scopus.com/inward/record.url?scp=85093105428&partnerID=8YFLogxK
U2 - 10.1016/j.msec.2020.111616
DO - 10.1016/j.msec.2020.111616
M3 - Article
C2 - 33321659
SN - 0928-4931
VL - 119
JO - Materials Science and Engineering C
JF - Materials Science and Engineering C
M1 - 111616
ER -
