<br>AXL 启动的 pSTAT3 旁分泌激活增强肿瘤相关巨噬细胞的间充质和血管生成支持特征,Cell Reports

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AXL 启动的 pSTAT3 旁分泌激活增强肿瘤相关巨噬细胞的间充质和血管生成支持特征
Cell Reports ( IF 7.5 ) Pub Date : 2023-09-01 , DOI: 10.1016/j.celrep.2023.113067
Chia-Nung Hung ₁ , Meizhen Chen ₁ , Daniel T DeArmond ₂ , Cheryl H-L Chiu ₁ , Catherine A Limboy ₁ , Xi Tan ₁ , Meena Kusi ₁ , Chih-Wei Chou ₁ , Li-Ling Lin ₁ , Zhao Zhang ₁ , Chiou-Miin Wang ₁ , Chun-Liang Chen ₃ , Kohzoh Mitsuya ₁ , Pawel A Osmulski ₁ , Maria E Gaczynska ₁ , Nameer B Kirma ₁ , Ratna K Vadlamudi ₄ , Don L Gibbons ₅ , Steve Warner ₆ , Andrew J Brenner ₇ , Daruka Mahadevan ₇ , Joel E Michalek ₈ , Tim H-M Huang ₉ , Josephine A Taverna ₁₀

Affiliation

Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USA.
Department of Cardiothoracic Surgery, University of Texas Health Science Center, San Antonio, TX, USA.
Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USA; Office of Nursing Research & Scholarship, School of Nursing, University of Texas Health Science Center, San Antonio, TX, USA.
Mays Cancer Center, University of Texas Health Science Center, San Antonio, TX, USA; Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, TX, USA.
Department of Thoracic, Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sumitomo Pharma Oncology, Inc, Lehi, UT, USA.
Mays Cancer Center, University of Texas Health Science Center, San Antonio, TX, USA; Division of Hematology and Oncology, Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA.
Department of Population Health Sciences, University of Texas Health Science Center, San Antonio, TX, USA.
Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USA; Mays Cancer Center, University of Texas Health Science Center, San Antonio, TX, USA.
Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USA; Mays Cancer Center, University of Texas Health Science Center, San Antonio, TX, USA; Division of Hematology and Oncology, Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA.

肿瘤相关巨噬细胞（TAM）是复杂肿瘤微环境（TME）发展中不可或缺的一部分，并且可以响应细胞外信号执行不同的细胞程序。然而，支撑这种表型可塑性的上游信号传导过程仍有待阐明。在这里，我们报告 TAM 中一致的 AXL-STAT3 信号传导是由细胞因子环境中的肺癌细胞或癌症相关成纤维细胞触发的。这种旁分泌作用驱动 TAM 分化为促进肿瘤的“M2 样”表型，并上调 CD163 和推定的间充质标记物，从而导致 TAM 异质性和多样化的细胞功能。 CD44 是上调标记之一，由 AXL-IL-11-pSTAT3 信号级联介导，增强巨噬细胞与内皮细胞相互作用的能力，促进原始血管网络的形成。我们还发现，AXL-STAT3 抑制可以阻止异种移植小鼠模型中 TAM 的募集，从而抑制肿瘤生长。这些发现表明 AXL-STAT3 相关标记物有可能应用于定量评估肺癌的转移潜力并为肺癌的治疗策略提供信息。

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更新日期：2023-09-01

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