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Updated: Jun 20, 2026
13:34
A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds
Published on: April 6, 2016
Elevated epithelial insulin-like growth factor expression is a risk factor for lung cancer development
Woo-Young Kim1, Quanri Jin, Seung-Hyun Oh
1Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Cancer Research
|September 10, 2009
Summary
Insulin-like growth factors (IGFs) in bronchial tissue, not serum, are linked to lung cancer development. Inhibiting the IGF-I receptor (IGF-IR) shows promise in controlling lung cancer, especially when combined with tobacco carcinogens.
Area of Science:
- Oncology
- Molecular Biology
- Carcinogenesis
Background:
- Insulin-like growth factor (IGF)-I receptor (IGF-IR) signaling is implicated in human neoplasms.
- The role of serum IGFs in lung cancer risk remains controversial.
- This study investigates the role of tissue-derived IGFs in lung carcinogenesis.
Purpose of the Study:
- To assess the role of tissue-derived IGFs in lung carcinogenesis.
- To evaluate the therapeutic potential of IGF-IR inhibitors in lung cancer.
- To understand the interaction between IGFs and tobacco carcinogens in lung cancer.
Main Methods:
- Quantified IGF-I and IGF-II levels in bronchial tissue specimens with varying degrees of dysplasia.
- Utilized human bronchial epithelial cell lines with KRAS(V12) mutation or p53 loss.
- Assessed the effects of IGF-IR inactivation, IGF inhibition, and IGF-IR overexpression on cell transformation.
- Evaluated the impact of tobacco carcinogens (TCs) on cell characteristics.
- Tested the antitumor activity of a selective IGF-IR tyrosine kinase inhibitor in vitro and in vivo models exposed to TCs.
Main Results:
- IGF-I and IGF-II levels were significantly higher in bronchial tissues with high-grade dysplasia compared to normal or hyperplastic tissues.
- Cell lines with KRAS(V12) or p53 loss overexpressed IGF-I and IGF-II.
- Inactivation of IGF-IR or inhibition of IGF expression suppressed transformed cell characteristics.
- Overexpression of IGF-IR or exposure to TCs enhanced transformed characteristics.
- The selective IGF-IR inhibitor demonstrated antitumor activity in vitro and in vivo.
Conclusions:
- Airway epithelial cells produce IGFs in an autocrine/paracrine manner, which cooperate with TCs to promote lung carcinogenesis.
- Targeting IGF-IR signaling with selective inhibitors represents a rational strategy for lung cancer control.
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