Stromal Expression of Activated Leukocyte Cell Adhesion Molecule Promotes Lung Tumor Growth and Metastasis.

Autor:	Willrodt AH; Institute of Pharmaceutical Sciences, ETH Zurich (Swiss Federal Institute of Technology), Zurich, Switzerland., Beffinger M; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Vranova M; Institute of Pharmaceutical Sciences, ETH Zurich (Swiss Federal Institute of Technology), Zurich, Switzerland., Protsyuk D; Institute of Physiology, University of Zurich, Zurich, Switzerland., Schuler K; Institute of Pharmaceutical Sciences, ETH Zurich (Swiss Federal Institute of Technology), Zurich, Switzerland., Jadhav M; Institute of Pharmaceutical Sciences, ETH Zurich (Swiss Federal Institute of Technology), Zurich, Switzerland., Heikenwalder M; Division of Chronic Inflammation and Cancer, German Cancer Research Center, Heidelberg, Germany., van den Broek M; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Borsig L; Institute of Physiology, University of Zurich, Zurich, Switzerland., Halin C; Institute of Pharmaceutical Sciences, ETH Zurich (Swiss Federal Institute of Technology), Zurich, Switzerland. Electronic address: cornelia.halin@pharma.ethz.ch.
Jazyk:	angličtina
Zdroj:	The American journal of pathology [Am J Pathol] 2017 Nov; Vol. 187 (11), pp. 2558-2569. Date of Electronic Publication: 2017 Aug 17.
DOI:	10.1016/j.ajpath.2017.07.008
Abstrakt:	Activated leukocyte cell adhesion molecule (ALCAM) is expressed on various cell types, including leukocytes, endothelial cells, and certain tumor cells. Although ALCAM expression on tumor cells has been linked to tumor invasion and metastatic spread, the contribution of ALCAM expressed in cells forming the tumor stroma to cancer progression has not been investigated. In this study, ALCAM-deficient (ALCAM -/- ) mice were used to evaluate the role of ALCAM in lung tumor growth and metastasis. ALCAM -/- mice displayed an altered blood vascular network in the lung and the diaphragm, indicative of an angiogenetic defect. The absence of ALCAM expression in cells forming the stromal tumor microenvironment profoundly affected lung tumor growth in three different i.v. metastasis models. In the case of Lewis lung carcinoma (LLC), an additional defect in tumor cell homing to the lungs and a resulting reduction in the number of lung tumor nodules were observed. Similarly, when LLC cells were implanted subcutaneously for the study of spontaneous tumor cell metastasis, the rate of LLC metastasis to the lungs was profoundly reduced in ALCAM -/- mice. Taken together, our work demonstrates for the first time the in vivo contribution of ALCAM to angiogenesis and reveals a novel role of stromally expressed ALCAM in supporting tumor growth and metastatic spread. (Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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