Lung cancer cell‐derived EDA‐containing fibronectin induces an inflammatory response from monocytes and promotes metastatic tumor microenvironment
Asif Amin, Taseem A. Mokhdomi, Shoiab Bukhari, Zubair Ahmad Wani, Naveed Anjum Chikan, Basit Amin Shah, Aabid Koul, Umer Majeed, Faizah Farooq, Ayub Qadri, Raies A. Qadri
Abstract
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 (EDA FN ) was identified as a conspicuous immunogenic protein in A549 cell secretome. We showed that A549 secreted EDA FN engages TLR‐4 on THP‐1 monocytes to drive the proinflammatory response via NF‐κB signaling cascade. Conversely, A549 derived EDA FN 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 EDA FN and resulting in the establishment of proinflammatory and metastatic tumor microenvironment.