Collagen-rich airway smooth muscle cells are a metastatic niche for tumor colonization in the lung

Yu Cheng Lee, Antonina V. Kurtova, Jing Xiao, Fotis Nikolos, Kazukuni Hayashi, Zoe Tramel, Antrix Jain, Fengju Chen, Mithil Chokshi, Ciaran Lee, Gang Bao, Xiang Zhang, Jianjun Shen, Qianxing Mo, Sung Yun Jung, David Rowley, Keith Syson Chan

    Research output: Contribution to journalArticlepeer-review

    25 Scopus citations

    Abstract

    Metastases account for the majority of cancer deaths. While certain steps of the metastatic cascade are well characterized, identification of targets to block this process remains a challenge. Host factors determining metastatic colonization to secondary organs are particularly important for exploration, as those might be shared among different cancer types. Here, we showed that bladder tumor cells expressing the collagen receptor, CD167a, responded to collagen I stimulation at the primary tumor to promote local invasion and utilized the same receptor to preferentially colonize at airway smooth muscle cells (ASMCs)—a rich source of collagen III in lung. Morphologically, COL3-CD167a-driven metastatic foci are uniquely distinct from typical lung alveolar metastatic lesions and exhibited activation of the CD167a-HSP90-Stat3 axis. Importantly, metastatic lung colonization could be abrogated using an investigational drug that attenuates Stat3 activity, implicating this seed-and-soil interaction as a therapeutic target for eliminating lung metastasis.

    Original languageEnglish (US)
    Article number2131
    JournalNature Communications
    Volume10
    Issue number1
    DOIs
    StatePublished - Dec 1 2019

    ASJC Scopus subject areas

    • Chemistry(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Physics and Astronomy(all)

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