Abstract 4658: Cigarette smoke extract and benzo(a)pyrene induce osteopontin expression in lung cancer and promote mesenchymal stem cell recruitment

Cigarette smoking produces many organic compounds, including the carcinogenic polycyclic aromatic hydrocarbon benzo(a)pyrene, (BAP), which is linked to lung cancer. Tumor tissue recruits mesenchymal stem cells (MSCs; undifferentiated multipotent adult stem cells) to increase cancer cell proliferation, invasion and metastasis. We sought to determine the effects of cigarette smoke extract (CSE) and BAP stimulation on lung cancer cells and MSCs. We found that CSE and BAP increased mRNA and protein expression of osteopontin (OPN), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) family, but had no such effects on any other SIBLINGs proteins. A National Center for Biotechnology Information (NCBI) analysis of data from the Gene Expression Omnibus (GEO) database (GSE31210) identified much higher OPN expression in current and ex-cigarette smokers with lung cancer than in lung cancer patients who were nonsmokers. Our analysis found that stimulating lung cancer cells with CSE and BAP led to the recruitment of MSCs, which adhered to lung cancer cells via OPN production. Next, we used a gene set from the BioCarta database to investigate signaling pathways associated with lung cancer. We found that the MAPK, JAK/STAT and RAS signaling pathways had the highest repeatability in lung cancer patients who were cigarette smokers. We discovered that CSE and BAP only activated the JAK2/STAT3 pathway and that transfection of lung cancer cells with JAK2 and STAT3 small interfering RNAs interrupted CSE- and BAP-induced OPN expression, inhibiting MSC recruitment and adhesion. We are now investigating whether MSCs link back to lung cancer cells and further induce migration and invasion. In summary, our data indicate that CSE and BAP increase OPN expression in lung cancer cells through the JAK2/STAT3 signaling pathway and thereby recruit MSCs and their adhesion to cancer cells. Citation Format: Ya-Jing Jiang, An-Chen Chang, Po-Chun Chen, Chih-Hsin Tang. Cigarette smoke extract and benzo(a)pyrene induce osteopontin expression in lung cancer and promote mesenchymal stem cell recruitment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4658.