Mesenchymal stem cell homing towards cancer cells is increased by enzyme activity of cathepsin D.
Exp Cell Res
; 383(1): 111494, 2019 10 01.
Article
em En
| MEDLINE
| ID: mdl-31306655
ABSTRACT
Mesenchymal stem cells home towards inflammatory microenvironments, such as the tumour stroma, where they have been shown to have both pro- and anti-tumorigenic effects. Here, we demonstrate that the aspartic acid protease cathepsin D is part of the chemoattraction process. Using a Boyden chamber co-culture system, the migration of the mesenchymal stem cells and their invasion through Matrigel increased in the presence of breast cancer MDA-MB-231â¯cells, colon cancer HT29â¯cells or their conditioned media. Mesenchymal stem cell movement was reduced by protease inhibitors of matrix metalloproteinases and by pepstatin A, an inhibitor of cathepsin D. We confirmed a role for cathepsin D through addition of recombinant protein, upregulation of cathepsin D release using chloroquine and knockdown of cathepsin D expression. While all cell types expressed active cathepsin D, enzymatically inactive precursor procathepsin D was expressed only at low levels by mesenchymal stem cells. Expression in mesenchymal stem cells was increased following co-culture with cancer cells. The chemoattractive effect of cathepsin D required its enzymatic activity, but not changes in mesenchymal stem cell proliferation or adhesion rates. In conclusion, cathepsin D and its precursors enhance mesenchymal stem cell homing towards tumour sites, most likely by enzymatic mechanisms.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Movimento Celular
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Catepsina D
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Neoplasias do Colo
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Precursores Enzimáticos
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Microambiente Tumoral
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Células-Tronco Mesenquimais
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article