Maru Yoshiro
   Department   School of Medicine, School of Medicine
   Position   Professor and Division head
Article types Review article
Language English
Peer review Non peer reviewed
Title The lung metastatic niche.
Journal Formal name：Journal of molecular medicine (Berlin, Germany)
Abbreviation：J Mol Med (Berl)
ISSN code：(1432-1440)0946-2716(Linking)
Domestic / ForeginForegin
Volume, Issue, Page 93(11),pp.1185-1192
Author and coauthor Maru Yoshiro
Authorship Lead author,Corresponding author
Publication date 2015/11
Summary Cancer cells that succeed in forming lung metastases need to survive in a foreign microenvironment and to protect themselves against immune surveillance. Lung metastatic niches facilitate this process. They can develop as pre-metastatic niches by inflammatory events that are provoked by primary tumors before tumor cell arrival, and/or they can be post-formed by reciprocal signaling between metastasizing tumor cells and local non-tumor cells. Primary tumor-derived factors induce expression of chemokines in the lungs to which bone marrow-derived myeloid cells are recruited. These cells work in concert with lung-specific resident cells to establish pre-metastatic niches. The role of the endogenous TLR4-dependent innate immune system in pre-metastatic niche formation illustrates this point. During lung infection, endotoxin induces inflammation by increasing vascular permeability and leukocyte mobilization to the lungs through the endotoxin receptor TLR4 that is expressed in endothelial cells and leukocytes, respectively. This innate immune system can be hijacked by primary tumors to generate a pre-metastatic niche. Specifically, primary tumor-produced chemokine CCL2 works in an endocrine manner to induce pulmonary overexpression of endogenous TLR4 ligands such as S100A8 and SAA3 resulting in lung inflammation similar to that caused by endotoxin. An endotoxin analog Eritoran inhibits pre-metastatic niche formation in this system.
DOI 10.1007/s00109-015-1355-2
PMID 26489606