RRC ID |
65122
|
著者 |
Kanzaki R, Naito H, Kise K, Takara K, Eino D, Minami M, Shintani Y, Funaki S, Kawamura T, Kimura T, Okumura M, Takakura N.
|
タイトル |
Gas6 derived from cancer-associated fibroblasts promotes migration of Axl-expressing lung cancer cells during chemotherapy.
|
ジャーナル |
Sci Rep
|
Abstract |
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.
|
巻・号 |
7(1)
|
ページ |
10613
|
公開日 |
2017-9-6
|
DOI |
10.1038/s41598-017-10873-2
|
PII |
10.1038/s41598-017-10873-2
|
PMID |
28878389
|
PMC |
PMC5587707
|
MeSH |
Aged
Animals
Axl Receptor Tyrosine Kinase
Biomarkers, Tumor
Cancer-Associated Fibroblasts / metabolism*
Cancer-Associated Fibroblasts / pathology
Cell Cycle
Cell Line, Tumor
Cell Movement / genetics
Cell Proliferation
Disease Models, Animal
Female
Gene Expression Regulation, Neoplastic*
Humans
Intercellular Signaling Peptides and Proteins / genetics
Intercellular Signaling Peptides and Proteins / metabolism*
Lung Neoplasms / drug therapy
Lung Neoplasms / genetics*
Lung Neoplasms / metabolism*
Lung Neoplasms / pathology
Male
Mice
Middle Aged
Neoplasm Staging
Proto-Oncogene Proteins / genetics*
Receptor Protein-Tyrosine Kinases / genetics*
Xenograft Model Antitumor Assays
|
IF |
3.998
|
リソース情報 |
ヒト・動物細胞 |
LLC(RCB0558) |