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Updated: Nov 23, 2025
Lung Tumor Cell Recruitment Assay
Published on: February 26, 2019
Lung cancer cell-derived EDA-containing fibronectin induces an inflammatory response from monocytes and promotes
Asif Amin1,2, Taseem A Mokhdomi1,3, Shoiab Bukhari1,4
1Department of Biotechnology, University of Kashmir, Srinagar, India.
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.
Insights
Lung cancer cells secrete fibronectin (EDAFN) that promotes tumor growth. This protein triggers inflammation and metastasis by interacting with monocytes and inducing epithelial-mesenchymal transition.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Tumor-associated macrophages (TAMs) promote tumor growth and metastasis through interactions with cancer cells.
- Tumor cell-secreted proteins in the tumor microenvironment mediate this crucial cross-talk.
Purpose of the Study:
- To investigate the molecular mechanisms underlying the cross-talk between lung cancer cells and TAMs.
- To identify specific tumor cell-secreted proteins involved in promoting a pro-tumorigenic microenvironment.
Main Methods:
- Immunoscreening of A549 lung carcinoma cell secretome using immunized Balb-c mice.
- Serological examination and mass spectrometry to identify immunogenic proteins.
- Analysis of EDAFN's interaction with THP-1 monocytes and its effect on NF-κB signaling and epithelial-mesenchymal transition.
Main Results:
- Fibronectin containing the extra-domain A (EDAFN) was identified as a key immunogenic protein secreted by A549 cells.
- A549-derived EDAFN activates Toll-like receptor 4 (TLR-4) on monocytes, initiating a pro-inflammatory response via NF-κB signaling.
- EDAFN exhibits autocrine activity, inducing epithelial-mesenchymal transition and enhancing the metastatic potential of lung cancer cells.
Conclusions:
- Lung cancer cells release EDAFN, which mediates cellular cross-talk with monocytes.
- EDAFN contributes to establishing a pro-inflammatory and pro-metastatic tumor microenvironment, driving tumor progression.
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