IGF1R acts as a cancer-promoting factor in the tumor microenvironment facilitating lung metastasis implantation and progression.
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
24
08
2021
accepted:
01
06
2022
revised:
27
05
2022
pubmed:
11
6
2022
medline:
14
7
2022
entrez:
10
6
2022
Statut:
ppublish
Résumé
Given the long-term ineffectiveness of current therapies and late-stage diagnoses, lung cancer is a leading cause of malignant diseases. Tumor progression is influenced by cancer cell interactions with the tumor microenvironment (TME). Insulin-like growth factor 1 receptor (IGF1R) was reported to affect the TME; however, the role of IGF1R in lung TME has not been investigated. First, we assessed IGF1R genomic alterations and expression in NSCLC patient tissue samples, as well as IGF1R serum levels. Next, we performed tumor heterotopic transplantation and pulmonary metastases in IGF1R-deficient mice using melanoma and Lewis lung carcinoma (LLC) cells. Herein we report increased amplification and mRNA expression, as well as increased protein expression (IGF1R/p-IGF1R) and IGF1R levels in tumor samples and serum from NSCLC patients, respectively. Moreover, IGF1R deficiency in mice reduced tumor growth, proliferation, inflammation and vascularization, and increased apoptosis after tumor heterotopic transplantation. Following induction of lung metastasis, IGF1R-deficient lungs also demonstrated a reduced tumor burden, and decreased expression of tumor progression markers, p-IGF1R and p-ERK1/2. Additionally, IGF1R-deficient lungs showed increased apoptosis and diminished proliferation, vascularization, EMT and fibrosis, along with attenuated inflammation and immunosuppression. Accordingly, IGF1R deficiency decreased expression of p-IGF1R in blood vessels, fibroblasts, tumor-associated macrophages and FOXP3
Identifiants
pubmed: 35688943
doi: 10.1038/s41388-022-02376-w
pii: 10.1038/s41388-022-02376-w
pmc: PMC9184253
doi:
Substances chimiques
Biomarkers, Tumor
0
IGF1R protein, human
0
Igf1r protein, mouse
0
Receptor, IGF Type 1
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3625-3639Informations de copyright
© 2022. The Author(s).
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