Interferon-Induced Transmembrane Protein 1 (IFITM1) Promotes Distant Metastasis of Small Cell Lung Cancer.
Adrenal Gland Neoplasms
/ secondary
Animals
Antigens, Differentiation
/ genetics
Bone Neoplasms
/ secondary
Carcinoma, Small Cell
/ genetics
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Heterografts
Humans
Lung Neoplasms
/ genetics
Mice
Mice, Nude
Neoplasm Invasiveness
Neoplasm Metastasis
/ genetics
Neoplasm Proteins
/ genetics
Neoplasm Transplantation
Organ Specificity
RNA Interference
RNA, Neoplasm
/ genetics
RNA, Small Interfering
/ genetics
IFITM1
experimental metastasis model
metastasis
orthotopic transplantation model
small cell lung cancer
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
13 Jul 2020
13 Jul 2020
Historique:
received:
19
06
2020
revised:
10
07
2020
accepted:
10
07
2020
entrez:
17
7
2020
pubmed:
17
7
2020
medline:
3
3
2021
Statut:
epublish
Résumé
Small cell lung cancer (SCLC) is a severe malignancy associated with early and widespread metastasis. To study SCLC metastasis, we previously developed an orthotopic transplantation model using the human SCLC cell line DMS273. In the model, metastatic foci were found in distant tissues such as bone and the adrenal gland, similarly as observed in patients with SCLC. In this study, we evaluated the differentially expressed genes between orthotopic and metastatic tumors in the model. We isolated tumor cells from orthotopic and metastatic sites, and the tumor cell RNA was analyzed using DNA microarray analysis. We found that 19 genes in metastatic tumors were upregulated by more than 4-fold compared with their expression in orthotopic tumors. One of these genes encodes a transmembrane protein, interferon (IFN)-induced transmembrane protein 1 (IFITM1), and immunohistochemical analysis confirmed the higher expression of the protein in metastatic sites than in orthotopic sites. IFITM1 was also detected in some SCLC cell lines and lung tumors from patients with SCLC. The overexpression of IFITM1 in DMS273 cells increased their metastatic formation in the orthotopic model and in an experimental metastasis model. Conversely, the silencing of IFITM1 suppressed metastatic formation by DMS273 cells. We also found that IFITM1 overexpression promoted the metastatic formation of NCI-H69 human SCLC cells. These results demonstrate that IFITM1 promotes distant metastasis in xenograft models of human SCLC.
Identifiants
pubmed: 32668617
pii: ijms21144934
doi: 10.3390/ijms21144934
pmc: PMC7404048
pii:
doi:
Substances chimiques
Antigens, Differentiation
0
Neoplasm Proteins
0
RNA, Neoplasm
0
RNA, Small Interfering
0
leu-13 antigen
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Japan Society for the Promotion of Science
ID : 26460481
Organisme : Japan Society for the Promotion of Science
ID : 17K08777
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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