PO.PR02.02 · 预防研究

预测和预防近地轨道中的癌症干性

Predicting and preventing cancer stemness in low Earth orbit

编号 7631 展板 18 时间 4/22 09:00–12:00 区域 Section 36 主讲 Jessica Pham

分会场 Cancer and Cancer Related Alterations, Detection Approaches, and Molecular Characterization

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作者与单位 Authors & Affiliations

Jessica Pham¹, Wenxue Ma¹, Claire Engstrom¹, Patrick Chang², Shuvro P. Nandi³, Inge van der Werf¹, Emma Klacking¹, Teresa Sposito¹, Kendale Wirtjes¹, Thomas Frias¹, Antonio Ruiz¹, Jane Isquith², Luisa Ladel¹, Christina N. Wu¹, Jana Stoudemire², Pinar Mesci⁴, Kay T. Yeung⁵, Rebecca A. Shatsky⁵, Anna A. Khachatrian⁶, James J. La Clair⁷, Michael D. Burkart⁷, Peggy Wentworth², Curtis L. Scribner⁸, Sheldon R. Morris², Thomas Whisenant⁹, Karla Mack², Ludmil B. Alexandrov¹⁰, Catriona H. M. Jamieson²

¹Department of Medicine, Division of Regenerative Medicine, UC San Diego, La Jolla, CA,²Sanford Stem Cell Institute, UC San Diego, La Jolla, CA,³Department of Cellular and Molecular Medicine, Department of Bioengineering, UC San Diego, La Jolla, CA,⁴Axiom Space, Houston, TX,⁵Department of Medicine, UC San Diego, La Jolla, CA,⁶Scripps Health, La Jolla, CA,⁷Department of Chemistry and Biochemistry, UC San Diego, La Jolla, CA,⁸Aspera Biomedicines, La Jolla, CA,⁹Center for Computational Biology and Bioinformatics, UC San Diego, La Jolla, CA,¹⁰Sanford Stem Cell Institute, Dept. of Cellular and Molecular Medicine, Depart. of Bioengineering, UC San Diego, La Jolla, CA

摘要 Abstract

中文摘要

癌症干性特性，包括增强的存活、恶性再生、端粒失调、基因组和表观转录组不稳定性，助推转移，并已被关联到应激、逆转录转座子和炎性细胞因子激活，这些可发生于近地轨道（LEO）中。在NASA Axiom 1、2和3执行的ISS任务中，对慢病毒FUCCI2BL细胞周期报告基因和ADAR1-GFP报告基因转导的红白血病（TF-1a）、结直肠癌（Caco-2）和转移性乳腺癌（MBC；MDA-MB-231及患者样本）进行共聚焦成像、WGS、RNA-seq和scRNA-seq，揭示了增殖、显著的基因组不稳定性、HERV和LINE-1逆转录转座子失调，以及APOBEC3C和ADAR1激活。此外，在Axiom 2和3任务中，使用表达ADAR1报告基因的MBC类器官及人源化MBC小鼠模型，一种ADAR1p150剪接调节剂rebecsinib（IND 153126）阻止了肿瘤扩增。因此，在LEO中开展癌症研究可能加速创新癌症治疗药物及长期太空飞行对策的开发。

查看英文原文 English abstract

Cancer stemness properties, including enhanced survival, malignant regeneration, telomere deregulation, genomic and epitranscriptomic instability, fuel metastases, and have been linked to stress, retrotransposon and inflammatory cytokine activation, which can occur in low earth orbit (LEO). In NASA Axiom 1, 2 and 3 missions to the ISS, confocal imaging, WGS, RNA-seq and scRNA-seq of lentiviral FUCCI2BL cell cycle and ADAR1-GFP reporter transduced erythroleukemia (TF-1a), colorectal (Caco-2) and metastatic breast cancer (MBC; MDA-MB-231 and patient samples) revealed proliferation, significant genomic instability, HERV and LINE-1 retrotransposon deregulation, and APOBEC3C and ADAR1 activation. Moreover, in Axiom 2 and 3 missions with ADAR1-reporter expressing MBC organoids and in humanized MBC mouse models, an ADAR1p150 splicing modulator, rebecsinib (IND 153126), prevented tumor propagation. Thus, cancer studies in LEO may accelerate the development of innovative cancer therapeutics and countermeasures for long-term spaceflight.

利益披露 Disclosure

J. Pham, None.. W. Ma, None.. C. Engstrom, None. P. Chang, Aspera Biomedicines Independent Contractor. S. P. Nandi, None.. I. van der Werf, None.. E. Klacking, None.. T. Sposito, None.. K. Wirtjes, None.. T. Frias, None.. A. Ruiz, None.. J. Isquith, None.. L. Ladel, None.. C. N. Wu, None.. J. Stoudemire, None. P. Mesci, Axiom Space Employment. K. T. Yeung, None.. R. A. Shatsky, None.. A. A. Khachatrian, None. J. J. La Clair, Aspera Biomedicines Employment. M. D. Burkart, Aspera Biomedicines Employment. P. Wentworth, Aspera Biomedicines Employment. C. L. Scribner, Aspera Biomedicines Employment. S. R. Morris, Aspera Biomedicines Co-Founder. T. Whisenant, None. K. Mack, Aspera Biomedicines Employment. L. B. Alexandrov, Acturion Employment. C. H. M. Jamieson, Aspera Biomedicines Co-Founder. Impact Biomedicines Co-Founder. Forty Seven Inc Royalties.

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