Molecular size-dependent specificity of hyaluronan on functional properties, morphology and matrix composition of mammary cancer cells.
BTH, bovine testes hyaluronidase
Breast cancer
CD44
ECM, extracellular matrix
EMT, epithelial-to-mesenchymal transition
ER, estrogen receptor
Epithelial-to-mesenchymal transition
Estrogen receptors
HA, hyaluronan or hyaluronic acid
HAS, hyaluronan synthase
HMW HA, high molecular weight hyaluronan
HYAL, hyaluronidase
Hyaluronan
LMW HA, low molecular weight hyaluronan
MET, mesenchymal-to-epithelial transition
MMPs, matrix metalloproteinases
SDC, syndecan
SEM, scanning electron microscopy
Scanning electron microscopy
TIMPs, tissue inhibitors of metalloproteinases
o-HA, hyaluronan oligomers
s-HA, sulfated hyaluronan
tPA, tissue plasminogen activator
uPA, urokinase plasminogen activator
Journal
Matrix biology plus
ISSN: 2590-0285
Titre abrégé: Matrix Biol Plus
Pays: Netherlands
ID NLM: 101775320
Informations de publication
Date de publication:
Aug 2019
Aug 2019
Historique:
received:
05
12
2018
revised:
28
05
2019
accepted:
29
05
2019
entrez:
5
2
2021
pubmed:
5
6
2019
medline:
5
6
2019
Statut:
epublish
Résumé
High levels of hyaluronan (ΗΑ), a major extracellular matrix (ECM) glycosaminoglycan, have been correlated with poor clinical outcome in several malignancies, including breast cancer. The high and low molecular weight HΑ forms exert diverse biological functions. Depending on their molecular size, ΗΑ forms either promote or attenuate signaling cascades that regulate cancer progression. In order to evaluate the effects of different ΗΑ forms on breast cancer cells' behavior, ΗΑ fragments of defined molecular size were synthesized. Breast cancer cells of different estrogen receptor (ER) status - the low metastatic, ERα-positive MCF-7 epithelial cells and the highly aggressive, ERβ-positive MDA-MB-231 mesenchymal cells - were evaluated following treatment with HA fragments. Scanning electron microscopy revealed that HA fragments critically affect the morphology of breast cancer cells in a molecular-size dependent mode. Moreover, the ΗΑ fragments affect cell functional properties, the expression of major ECM mediators and epithelial-to-mesenchymal transition (ΕΜΤ) markers. Notably, treatment with 200 kDa ΗΑ increased the expression levels of the epithelial marker Ε-cadherin and reduced the expression levels of HA synthase 2 and mesenchymal markers, like fibronectin and snail2/slug. These novel data suggest that the effects of HA in breast cancer cells depend on the molecular size and the ER status. An in-depth understanding on the mechanistic basis of these effects may contribute on the development of novel therapeutic strategies for the pharmacological targeting of aggressive breast cancer.
Identifiants
pubmed: 33543007
doi: 10.1016/j.mbplus.2019.100008
pii: S2590-0285(19)30007-9
pmc: PMC7852304
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100008Informations de copyright
© 2019 Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Carlo Barbera, Mauro Pavan and Devis Galesso were, at the time of the study, full-time employees at Fidia Farmaceutici S.p.A.
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