Lung cancer cell-derived EDA-containing fibronectin induces an inflammatory response from monocytes and promotes metastatic tumor microenvironment.
J Cell Biochem
; 122(5): 562-576, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-33393138
ABSTRACT
Tumor-associated macrophages (TAMs) play a pivotal role in facilitating tumor growth and metastasis. This tumor-promoting propensity of TAMs sets in as a result of their complex cross-talk with tumor cells mediated primarily by tumor cell-secreted proteins in the tumor microenvironment. To explore such interactions, we employed an immunoscreening approach involving the immunization of Balb-c mice with model human lung carcinoma cell line, A549. From serological examination combined with mass spectrometric analysis, EDA-containing fibronectin (EDAFN ) was identified as a conspicuous immunogenic protein in A549 cell secretome. We showed that A549 secreted EDAFN engages TLR-4 on THP-1 monocytes to drive the proinflammatory response via NF-κB signaling cascade. Conversely, A549 derived EDAFN potentiates their metastatic capacity by inducing epithelial-mesenchymal transition through its autocrine activity. In conclusion, the study proposes a possible mechanism of cellular cross-talk between lung cancer cells and associated monocytes mediated by lung cancer-derived EDAFN and resulting in the establishment of proinflammatory and metastatic tumor microenvironment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Monócitos
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Fibronectinas
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Neoplasias Pulmonares
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article