Biglycan as a potential regulator of tumorgenicity and immunogenicity in K-RAS-transformed cells.
Oncoimmunology
; 11(1): 2069214, 2022.
Article
em En
| MEDLINE
| ID: mdl-35529675
ABSTRACT
The extracellular matrix component biglycan (BGN) plays an essential role in various physiological and pathophysiological processes. A deficient BGN expression associated with reduced immunogenicity was found in HER-2/neu-overexpressing cells. To determine whether BGN is suppressed by oncogene-driven regulatory networks, the expression and function of BGN was analyzed in murine and human BGNlow/BGNhigh K-RASG12V-transformed model systems as well as in different patients' datasets of colorectal carcinoma (CRC) lesions. K-RAS-mutated CRC tissues expressed low BGN mRNA and protein levels when compared to normal colon epithelial cells, which was associated with a reduced patients' survival. Transfection of BGN in murine and human BGNlow K-RAS-expressing cells resulted in a reduced growth and migration of BGNhigh vs BGNlow K-RAS cells. In addition, increased MHC class I surface antigens as a consequence of an enhanced antigen processing machinery component expression was found upon restoration of BGN, which was confirmed by RNA-sequencing of BGNlow vs. BGNhigh K-RAS models. Furthermore, a reduced tumor formation of BGNhigh versus BGNlow K-RAS-transformed fibroblasts associated with an enhanced MHC class I expression and an increased frequency of tumor-infiltrating lymphocytes in tumor lesions was found. Our data provide for the first time an inverse link between BGN and K-RAS expression in murine and human K-RAS-overexpressing models and CRC lesions associated with altered growth properties, reduced immunogenicity and worse patients' outcome. Therefore, reversion of BGN might be a novel therapeutic option for K-RAS-associated malignancies.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
/
Fibroblastos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Oncoimmunology
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Alemanha