Format

Send to

Choose Destination
Nat Commun. 2019 May 13;10(1):2131. doi: 10.1038/s41467-019-09878-4.

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

Author information

1
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
2
Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.
3
Department of Biochemistry and Molecular Biology, Mass Spectrometry Proteomics Core, Baylor College of Medicine, Houston, TX, 77030, USA.
4
Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
5
Department of Bioengineering, Rice University Houston, Houston, TX, 77030, USA.
6
University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA.
7
Department of Biostatistics & Bioinformatics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.
8
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA. keithsyson2819@gmail.com.
9
Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA. keithsyson2819@gmail.com.

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.

PMID:
31086186
PMCID:
PMC6513865
DOI:
10.1038/s41467-019-09878-4
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center