文献类型：期刊文献

英文题名：Mesenchymal stem cells promote erlotinib resistance in non-small cell lung cancer through the HGF-AKT/ERK1/2-OPN pathway

作者：Yang, Yue[1,2];He, Jianxin[3];Long, Feng[3];Liu, Yongqi[3];Lin, Li[4];Wei, Hulai[2]

第一作者：Yang, Yue

通信作者：Wei, HL[1]

机构：[1]Northwest Minzu Univ, State Ethn Affairs Commiss, Key Lab Environm Ecol & Populat Hlth Northwest Min, Lanzhou 730000, Gansu, Peoples R China;[2]Lanzhou Univ, Sch Basic Med Sci, Key Lab Preclin Study New Drugs Gansu Prov, 199 Donggang West Rd, Lanzhou 730000, Gansu, Peoples R China;[3]Gansu Univ Chinese Med, Key Lab Minist Educ Dunhuang Med & Transformat, Lanzhou 730000, Gansu, Peoples R China;[4]Gansu Prov Matern & Child Care Hosp, Dept Hematol & Oncol, Lanzhou 730050, Gansu, Peoples R China

第一机构：Northwest Minzu Univ, State Ethn Affairs Commiss, Key Lab Environm Ecol & Populat Hlth Northwest Min, Lanzhou 730000, Gansu, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Sch Basic Med Sci, Key Lab Preclin Study New Drugs Gansu Prov, 199 Donggang West Rd, Lanzhou 730000, Gansu, Peoples R China.

年份：2025

卷号：17

期号：7

起止页码：4952

外文期刊名：AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001542299700002)】；

基金：This work was supported by the National Natural Science Foundation of China [number 81503377] , Industry Support Plan Project of Gansu Provincial Department of Education [number 2022CYZC-54] and Open Foundation of Key Laboratory of Dunhuang Medicine and Transformation [number DHYX18-10] , Scien-tific Research Fund for Talent Introduction of Northwest Minzu University [number xbmuy-jrc202235] , the Fundamental Research Funds for the Central Universities [number 31920-250061] and the University Fund for Young Doctors of Gansu Province [number 2022QB-027] .

语种：英文

外文关键词：Mesenchymal stem cells; HCC827; erlotinib resistance; HGF-AKT/ERK1/2 signals; osteopontin

摘要：Objectives: To investigate the mechanisms by which mesenchymal stem cells (MSCs) contribute to erlotinib resistance in non-small cell lung cancer (NSCLC). Methods: HCC827 NSCLC cells were treated with MSC-conditioned medium (MSC-CM). Cell viability and apoptosis were evaluated using MTT assays and flow cytometry, respectively. Protein and mRNA expression levels were assessed by western blotting and quantitative real-time PCR. For in vivo validation, a xenograft model was established by co-injecting HCC827 cells and MSCs into NOD/SCID mice. Results: MSC-CM significantly increased cell viability and reduced apoptosis in HCC827 cells following erlotinib treatment, indicating enhanced drug resistance. Mechanistically, MSC-secreted hepatocyte growth factor (HGF) activated AKT and ERK1/2 phosphorylation, thereby bypassing EGFR inhibition by erlotinib. Neutralization of HGF restored erlotinib sensitivity in MSC-CM-treated HCC827 cells. Furthermore, osteopontin (OPN) was transcriptionally upregulated and acted as a resistance enhancer. Inhibition of OPN attenuated MSC-CM-mediated resistance. In vivo, tumors derived from co-injected MSCs and HCC827 cells exhibited significantly greater volume and weight after erlotinib treatment compared to control tumors. Conclusions: This study identifies a novel MSC-mediated resistance mechanism in which MSC-derived HGF activates compensatory AKT/ERK1/2 signaling, circumventing EGFR blockade by erlotinib. Concurrent upregulation of OPN in NSCLC cells forms a synergistic survival axis under erlotinib pressure. These findings suggest that targeting MSC-derived HGF and tumor-derived OPN may offer promising strategies to overcome erlotinib resistance in NSCLC.