Lung cancer cell-derived EDA-containing fibronectin induces an inflammatory response from monocytes and promotes metastatic tumor microenvironment

© 2020 Wiley Periodicals LLC..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:122

Enthalten in:

Journal of cellular biochemistry - 122(2021), 5 vom: 01. Mai, Seite 562-576

Sprache:

Englisch

Beteiligte Personen:

Amin, Asif [VerfasserIn]
Mokhdomi, Taseem A [VerfasserIn]
Bukhari, Shoiab [VerfasserIn]
Wani, Zubair [VerfasserIn]
Chikan, Naveed A [VerfasserIn]
Shah, Basit A [VerfasserIn]
Koul, Aabid M [VerfasserIn]
Majeed, Umer [VerfasserIn]
Farooq, Faizah [VerfasserIn]
Qadri, Ayub [VerfasserIn]
Qadri, Raies A [VerfasserIn]

Links:

Volltext

Themen:

Fibronectin
Fibronectins
Inflammation
Journal Article
Metastasis
Research Support, Non-U.S. Gov't
Secretome
Tumor microenvironment

Anmerkungen:

Date Completed 04.10.2021

Date Revised 04.10.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1002/jcb.29883

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM319571343