ArticlePloS one2012
Small interfering RNA targeted to IGF-IR delays tumor growth and induces proinflammatory cytokines in a mouse breast cancer model.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Comparative study and meta-analysis of meta-analysis studies for the correlation of genomic markers with early cancer detection.Human genomics · 2013Pooled it
- IGF-1R inhibitors in cancer: A review of available evidence and future outlook.Critical reviews in oncology/hematology · 2025Review
- Decoding the Role of Insulin-like Growth Factor 1 and Its Isoforms in Breast Cancer.International journal of molecular sciences · 2024Review
- Extracellular Interactors of the IGF System: Impact on Cancer Hallmarks and Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Manipulating the tumor immune microenvironment to improve cancer immunotherapy: IGF1R, a promising target.Frontiers in immunology · 2024Review
- Drugging IGF-1R in cancer: New insights and emerging opportunities.Genes & diseases · 2023Review
- The Interplay Between Non-coding RNAs and Insulin-Like Growth Factor Signaling in the Pathogenesis of Neoplasia.Frontiers in cell and developmental biology · 2021Review
- Role of the IGF-1 Axis in Overcoming Resistance in Breast Cancer.Frontiers in cell and developmental biology · 2021Review
- MicroRNA‑98 suppresses cell growth and invasion of retinoblastoma via targeting the IGF1R/k‑Ras/Raf/MEK/ERK signaling pathway.International journal of oncology · 2019Article
- Loss of neutrophil polarization in colon carcinoma liver metastases of mice with an inducible, liver-specific IGF-I deficiency.Oncotarget · 2018Article
- Enhanced response of melanoma cells to MEK inhibitors following unbiased IGF-1R down-regulation.Oncotarget · 2017Article
- Citrate Suppresses Tumor Growth in Multiple Models through Inhibition of Glycolysis, the Tricarboxylic Acid Cycle and the IGF-1R Pathway.Scientific reports · 2017Article
- Inhibition of the insulin-like growth factor-1 receptor potentiates acute effects of castration in a rat model for prostate cancer growth in bone.Clinical & experimental metastasis · 2017Article
- The insulin-like growth factor-I receptor (IGF-IR) in breast cancer: biology and treatment strategies.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Sustained proliferation in cancer: Mechanisms and novel therapeutic targets.Seminars in cancer biology · 2015Review
- Evasion of anti-growth signaling: A key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds.Seminars in cancer biology · 2015Review
- Enhancement of glioma-specific immunity in mice by "NOBEL", an insulin-like growth factor 1 receptor antisense oligodeoxynucleotide.Cancer immunology, immunotherapy : CII · 2015Article
- MicroRNAs and Potential Targets in Osteosarcoma: Review.Frontiers in pediatrics · 2015Review
- Engineered ubiquitin ligase PTB-U-box targets insulin/insulin-like growth factor receptor for degradation and coordinately inhibits cancer malignancy.Oncotarget · 2014Article
- Redundant kinase activation and resistance of EGFR-tyrosine kinase inhibitors.American journal of cancer research · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Insulin-like growth factor I (IGF-I) and its type I receptor (IGF-IR) play significant roles in tumorigenesis and in immune response. Here, we wanted to know whether an RNA interference approach targeted to IGF-IR could be used for specific antitumor immunostimulation in a breast cancer model. For that, we evaluated short interfering RNA (siRNAs) for inhibition of in vivo tumor growth and immunological stimulation in immunocompetent mice. We designed 2'-O-methyl-modified siRNAs to inhibit expression of IGF-IR in two murine breast cancer cell lines (EMT6, C4HD). Cell transfection of IGF-IR siRNAs decreased proliferation, diminished phosphorylation of downstream signaling pathway proteins, AKT and ERK, and caused a G0/G1 cell cycle block. The IGF-IR silencing also induced secretion of two proinflammatory cytokines, TNF- α and IFN-γ. When we transfected C4HD cells with siRNAs targeting IGF-IR, mammary tumor growth was strongly delayed in syngenic mice. Histology of developing tumors in mice grafted with IGF-IR siRNA treated C4HD cells revealed a low mitotic index, and infiltration of lymphocytes and polymorphonuclear neutrophils, suggesting activation of an antitumor immune response. When we used C4HD cells treated with siRNA as an immunogen, we observed an increase in delayed-type hypersensitivity and the presence of cytotoxic splenocytes against wild-type C4HD cells, indicative of evolving immune response. Our findings show that silencing IGF-IR using synthetic siRNA bearing 2'-O-methyl nucleotides may offer a new clinical approach for treatment of mammary tumors expressing IGF-IR. Interestingly, our work also suggests that crosstalk between IGF-I axis and antitumor immune response can mobilize proinflammatory cytokines.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.