BMSC-derived leptin and IGFBP2 promote erlotinib resistance in lung adenocarcinoma cells through IGF-1R activation in hypoxic environment.

In this study, the effect of hypoxic cancer microenvironment in the bypass signaling activation was investigated. We found that bone marrow-derived mesenchymal stem cells (BMSCs) residing in the hypoxic solid cancer microenvironment highly produced molecules associated with adipocytes including adipokine leptin and IGFBPs. Leptin could induce the resistance of lung cancer cells to erlotinib through activating IGF-1R signaling. IGFBP2 counteracted the activation role of IGF-1 and induced erlotinib resistance by activating IGF-1R signaling in an IGF-1 independent manner. IGFBP2 had synergistic effect with leptin to induce erlotinib resistance. Leptin and IGFBP2 may be predictive factors for acquired resistance for EGFR-TKIs. PMID: 31559898 [PubMed - as supplied by publisher]
Source: Cancer Biology and Therapy - Category: Cancer & Oncology Authors: Tags: Cancer Biol Ther Source Type: research