Targeting LAYN inhibits colorectal cancer metastasis and tumor-associated macrophage infiltration induced by hyaluronan oligosaccharides.
Matrix Biol
; 117: 15-30, 2023 03.
Article
en En
| MEDLINE
| ID: mdl-36805871
ABSTRACT
The accumulation of hyaluronan oligosaccharides (oHA) in colorectal cancer (CRC) is closely related to tumor metastasis, but the underlying mechanism remains unclear. In this study, we first described that LAYN, a novel HA receptor, was upregulated in CRC tissue. Aberrant LAYN expression correlated with CRC metastasis and poor prognosis and positively correlated with tumor-associated macrophage (TAM) infiltration and M2 macrophage polarization in the tumor environment. Both in vitro and in vivo studies demonstrated that LAYN is activated by oHA and subsequently induces CRC metastasis and macrophage infiltration. Mechanistic studies demonstrated that oHA activates LAYN by binding to the 60-68th amino acid region of the extracellular segment. oHA-induced LAYN activation promoted metastasis and CCL20 secretion through the NF-kB pathway in CRC cells. Furthermore, targeting LAYN using a blocking antibody prevented oHA-mediated tumor metastasis, TAM infiltration and M2 polarization. This study revealed the LAYN activation mechanism and identified a potential target for the treatment of CRC tumor exhibiting high oHA levels.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
/
Macrófagos Asociados a Tumores
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Matrix Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
China