caa a22 4500 605544085 CHVBK 20210128100929.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s00109-015-1355-2 doi (NATIONALLICENCE)springer-10.1007/s00109-015-1355-2 Maru Yoshiro Department of Pharmacology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, 162-8666, Tokyo, Japan aut The lung metastatic niche [Elektronische Daten] [Yoshiro Maru] 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. Springer-Verlag Berlin Heidelberg, 2015 Lung nationallicence Metastasis nationallicence Niche nationallicence TLR4 nationallicence MD-2 nationallicence S100A8 nationallicence Journal of Molecular Medicine Springer Berlin Heidelberg 93/11(2015-11-01), 1185-1192 0946-2716 93:11<1185 2015 93 109 https://doi.org/10.1007/s00109-015-1355-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00109-015-1355-2 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Maru Yoshiro Department of Pharmacology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, 162-8666, Tokyo, Japan aut NATIONALLICENCE 773 0- Journal of Molecular Medicine Springer Berlin Heidelberg 93/11(2015-11-01), 1185-1192 0946-2716 93:11<1185 2015 93 109