Header

UZH-Logo

Maintenance Infos

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


Willrodt, Ann-Helen; Beffinger, Michal; Vranova, Martina; Protsyuk, Darya; Schuler, Katja; Jadhav, Maria; Heikenwalder, Mathias; van den Broek, Maries; Borsig, Lubor; Halin, Cornelia (2017). Stromal Expression of Activated Leukocyte Cell Adhesion Molecule Promotes Lung Tumor Growth and Metastasis. American Journal of Pathology, 187(11):2558-2569.

Abstract

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.

Abstract

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.

Statistics

Citations

Dimensions.ai Metrics
2 citations in Web of Science®
1 citation in Scopus®
1 citation in Microsoft Academic
Google Scholar™

Altmetrics

Downloads

13 downloads since deposited on 28 Dec 2017
12 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Uncontrolled Keywords:Pathology and Forensic Medicine
Language:English
Date:November 2017
Deposited On:28 Dec 2017 08:32
Last Modified:01 Nov 2018 01:29
Publisher:Elsevier
ISSN:0002-9440
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.ajpath.2017.07.008
Official URL:http://www.sciencedirect.com/science/article/pii/S0002944017303309
PubMed ID:28822802
Project Information:
  • : FunderSNSF
  • : Grant ID310030_138330
  • : Project TitleElucidating the impact of inflammation on lymphatic vessel function and on the induction of adaptive immunity
  • : FunderSNSF
  • : Grant ID310030_156269
  • : Project TitleElucidating the mechanism and the functional significance of leukocyte migration through afferent lymphatic vessels

Download

Download PDF  'Stromal Expression of Activated Leukocyte Cell Adhesion Molecule Promotes Lung Tumor Growth and Metastasis'.
Preview
Content: Accepted Version
Filetype: PDF
Size: 8MB
View at publisher