@article{oai:kanazawa-u.repo.nii.ac.jp:00056714,
 author = {内藤, 尚道 and 高倉, 伸幸 and Ryu Kanzaki, and Naito, Hisamichi and Kise, Kazuyoshi and Takara, Kazuhiro and Eino, Daisuke and Minami, Masato and Shintani, Yasushi and Funaki, Soichiro and Kawamura, Tomohiro and Kimura, Toru and Okumura, Meinoshin and Takakura, Nobuyuki},
 issue = {1},
 journal = {Scientific Reports},
 month = {Sep},
 note = {Alterations to the tumor stromal microenvironment induced by chemotherapy could influence the behavior of cancer cells. In the tumor stromal microenvironment, cancer-associated fibroblasts (CAFs) play an important role. Because the receptor tyrosine kinase Axl and its ligand Gas6 could be involved in promoting non-small cell lung cancer (NSCLC), we investigated the role of Gas6 secreted by CAFs during chemotherapy in NSCLC. In a murine model, we found that Gas6 expression by CAFs was upregulated following cisplatin treatment. Gas6 expression might be influenced by intratumoral hypoperfusion during chemotherapy, and it increased after serum starvation in a human lung CAF line, LCAFhTERT. Gas6 is associated with LCAFhTERT cell growth. Recombinant Gas6 promoted H1299 migration, and conditioned medium (CM) from LCAFhTERT cells activated Axl in H1299 cells and promoted migration. Silencing Gas6 in LCAFhTERT reduced the Axl activation and H1299 cell migration induced by CM from LCAFhTERT. In clinical samples, stromal Gas6 expression increased after chemotherapy. Five-year disease-free survival rates for patients with tumor Axl- and stromal Gas6-positive tumors (n = 37) was significantly worse than for the double negative group (n = 12) (21.9% vs 51.3%, p = 0.04). Based on these findings, it is presumed that Gas6 derived from CAFs promotes migration of Axl-expressing lung cancer cells during chemotherapy and is involved in poor clinical outcome. © 2017 The Author(s)., 金沢大学医薬保健研究域医学系},
 title = {Gas6 derived from cancer-associated fibroblasts promotes migration of Axl-expressing lung cancer cells during chemotherapy},
 volume = {7},
 year = {2017}
}