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作者

Shuyun Wang, Jing Wang, Wenjing Gong, Fang Zhang, Xiaozheng Chen, Huijun Xu, Yali Han, Xuebing Fu, Leirong Wang, Juan Li, Aiqin Gao, Yuping Sun

作者单位

Affiliations ¹ Phase I Clinical Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China. ² Medical Research & Laboratory Diagnostic Center, Central Hospital affiliated to Shandong First Medical University, Jinan, Shandong, China. ³ Department of Oncology, Yantai Yuhuangding Hospital, Medical College, Qingdao University, Yantai, Shandong, China. ⁴ Department of Oncology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China. ⁵ Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China. ⁶ Department of Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China. ⁷ Department of Radiation Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China. ⁸ Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China. ⁹ Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

刊名

Cancer science

年份

2024

ISSN

1349-7006

关键词

MMP-9 NSCLC VEGF-A angiogenesis immunoglobulin-like transcript 4.

摘要

Antiangiogenic therapy targeting VEGF-A has become the standard of first-line therapy for non-small cell lung cancer . However, its clinical response rate is still less than 50%, and most patients eventually develop resistance, even when using combination therapy with chemotherapy. The major cause of resistance is the activation of complex bypass signals that induce angiogenesis and tumor progression. Therefore, exploring novel proangiogenic mechanisms and developing promising targets for combin...更多

Antiangiogenic therapy targeting VEGF-A has become the standard of first-line therapy for non-small cell lung cancer . However, its clinical response rate is still less than 50%, and most patients eventually develop resistance, even when using combination therapy with chemotherapy. The major cause of resistance is the activation of complex bypass signals that induce angiogenesis and tumor progression. Therefore, exploring novel proangiogenic mechanisms and developing promising targets for combination therapy are crucial for improving the efficacy of antiangiogenic therapy. Immunoglobulin-like transcript 4 is a classic immunosuppressive molecule that inhibits myeloid cell activation. Recent studies have shown that tumor cell-derived ILT4 drives tumor progression via the induction of malignant biologies and creation of an immunosuppressive microenvironment. However, whether and how ILT4 participates in NSCLC angiogenesis remain elusive. Herein, we found that enriched ILT4 in NSCLC is positively correlated with high microvessel density, advanced disease, and poor overall survival. Tumor cell-derived ILT4 induced angiogenesis both in vitro and in vivo and tumor progression and metastasis in vivo. Mechanistically, ILT4 was upregulated by its ligand angiopoietin-like protein 2 . Their interaction subsequently activated the ERK1/2 signaling pathway to increase the secretion of the proangiogenic factors VEGF-A and MMP-9, which are responsible for NSCLC angiogenesis. Our study explored a novel mechanism for ILT4-induced tumor progression and provided a potential target for antiangiogenic therapy in NSCLC.收起

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