Trypsin is produced by and activates protease-activated receptor-2 in human cancer colon cells: evidence for new autocrine loop.
Life Sci
; 70(12): 1359-67, 2002 Feb 08.
Article
em En
| MEDLINE
| ID: mdl-11883712
ABSTRACT
In this work, we showed that human colon cancer cell lines produce trypsin which can activate a receptor for trypsin, the protease-activated receptor-2 (PAR-2), in these cells. RT-PCR experiments showed that trypsinogen transcripts were present in four colon cancer cell lines T84, Caco-2, HT-29 and C1.19A. By Western blot analysis we found a 25 kDa immunoreactive band identified as trypsinogen I in cell lysates and in the corresponding culture media. Concentrations of trypsin in cell media were found in nanomolar range, thus compatible with activation of protease-activated receptor 2 (PAR-2). This was further demonstrated in a colon cancer cell line (H-29) Ca2+i assay since increases in Ca2+i were observed in response to media from T84, Caco-2 or C1.19A cells that were similar to that observed with 2-5 nM trypsin and were abolished by trypsin inhibitor. Altogether, these data show that colon cancer cell lines produce and secrete trypsin at concentrations compatible with activation of PAR-2. They support possible autocrine/paracrine regulation of PAR-2 activity by trypsin in colon cancer cells.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tripsina
/
Receptores de Trombina
/
Neoplasias do Colo
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Life Sci
Ano de publicação:
2002
Tipo de documento:
Article