TY - JOUR
T1 - Collagen-rich airway smooth muscle cells are a metastatic niche for tumor colonization in the lung
AU - Lee, Yu Cheng
AU - Kurtova, Antonina V.
AU - Xiao, Jing
AU - Nikolos, Fotis
AU - Hayashi, Kazukuni
AU - Tramel, Zoe
AU - Jain, Antrix
AU - Chen, Fengju
AU - Chokshi, Mithil
AU - Lee, Ciaran
AU - Bao, Gang
AU - Zhang, Xiang
AU - Shen, Jianjun
AU - Mo, Qianxing
AU - Jung, Sung Yun
AU - Rowley, David
AU - Chan, Keith Syson
N1 - Funding Information:
This work was supported by NCI R01-CA175397 (KSC), CPRIT RP140252, V Foundation V Scholar Award (KSC), and in part by CPRIT Core Facility Support Awards: RP120348 and RP170002, CPRIT Core Facility Award: RP170005 and P30 Cancer Center support Grant: NCI-CA125123. We would like to thank the generosity of Dr. Y.H. Tsang and the late Dr. Kenneth Scott in providing the pHAGE-V5 vector, Dr. H. Kang in experimental assistance, and the technical assistance from Dr. Zhang, Ms. J. Liu and Dr. Nakada’s groups during manuscript revision.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-019-09878-4
DO - 10.1038/s41467-019-09878-4
M3 - Article
C2 - 31086186
AN - SCOPUS:85065719633
SN - 2041-1723
VL - 10
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2131
ER -