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dc.contributor.author
Regev, Ofer
dc.contributor.author
Kizner, Marina
dc.contributor.author
Roncato, Francesco
dc.contributor.author
Dadiani, Maya
dc.contributor.author
Saini, Massimo
dc.contributor.author
Castro-Giner, Francesc
dc.contributor.author
Yajuk, Olga
dc.contributor.author
Kozlovski, Stav
dc.contributor.author
Levi, Nehora
dc.contributor.author
Addadi, Yoseph
dc.contributor.author
Golani, Ofra
dc.contributor.author
Ben-Dor, Shifra
dc.contributor.author
Granot, Zvi
dc.contributor.author
Aceto, Nicola
dc.contributor.author
Alon, Ronen
dc.date.accessioned
2022-08-09T07:28:58Z
dc.date.available
2022-08-05T03:12:41Z
dc.date.available
2022-08-09T07:28:58Z
dc.date.issued
2022-07-11
dc.identifier.issn
1664-3224
dc.identifier.other
10.3389/fimmu.2022.849701
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/562059
dc.identifier.doi
10.3929/ethz-b-000562059
dc.description.abstract
Breast tumors and their derived circulating cancer cells express the leukocyte β2 integrin ligand Intercellular adhesion molecule 1 (ICAM-1). We found that elevated ICAM-1 expression in breast cancer cells results in a favorable outcome and prolonged survival of breast cancer patients. We therefore assessed the direct in vivo contribution of ICAM-1 expressed by breast cancer cells to breast tumorigenesis and lung metastasis in syngeneic immunocompetent mice hosts using spontaneous and experimental models of the lung metastasis of the C57BL/6-derived E0771 cell line, a luminal B breast cancer subtype. Notably, the presence of ICAM-1 on E0771 did not alter tumor growth or the leukocyte composition in the tumor microenvironment. Interestingly, the elimination of Tregs led to the rapid killing of primary tumor cells independently of tumor ICAM-1 expression. The in vivo elimination of a primary E0771 tumor expressing the ovalbumin (OVA) model neoantigen by the OVA-specific OVA-tcr-I mice (OT-I) transgenic cytotoxic T lymphocytes (CTLs) also took place normally in the absence of ICAM-1 expression by E0771 breast cancer target cells. The whole lung imaging of these cells by light sheet microscopy (LSM) revealed that both Wild type (WT)- and ICAM-1-deficient E0771 cells were equally disseminated from resected tumors and accumulated inside the lung vasculature at similar magnitudes. ICAM-1-deficient breast cancer cells developed, however, much larger metastatic lesions than their control counterparts. Strikingly, the vast majority of these cells gave rise to intravascular tumor colonies both in spontaneous and experimental metastasis models. In the latter model, ICAM-1 expressing E0771- but not their ICAM-1-deficient counterparts were highly susceptible to elimination by neutrophils adoptively transferred from E0771 tumor-bearing donor mice. Ex vivo, neutrophils derived from tumor-bearing mice also killed cultured E0771 cells via ICAM-1-dependent interactions. Collectively, our results are a first indication that ICAM-1 expressed by metastatic breast cancer cells that expand inside the lung vasculature is involved in innate rather than in adaptive cancer cell killing. This is also a first indication that the breast tumor expression of ICAM-1 is not required for CTL-mediated killing but can function as a suppressor of intravascular breast cancer metastasis to lungs.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Frontiers Media
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
adhesion
en_US
dc.subject
killing
en_US
dc.subject
metastasis
en_US
dc.subject
integrins
en_US
dc.subject
neutrophils
en_US
dc.subject
vasculature
en_US
dc.title
ICAM-1 on Breast Cancer Cells Suppresses Lung Metastasis but Is Dispensable for Tumor Growth and Killing by Cytotoxic T Cells
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
Frontiers in Immunology
ethz.journal.volume
13
en_US
ethz.journal.abbreviated
Front Immunol
ethz.pages.start
849701
en_US
ethz.size
19 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Lausanne
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02539 - Institut für Molecular Health Sciences / Institute of Molecular Health Sciences::09736 - Aceto, Nicola / Aceto, Nicola
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02539 - Institut für Molecular Health Sciences / Institute of Molecular Health Sciences::09736 - Aceto, Nicola / Aceto, Nicola
ethz.date.deposited
2022-08-05T03:12:43Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2022-08-09T07:29:09Z
ethz.rosetta.lastUpdated
2024-02-02T17:48:42Z
ethz.rosetta.versionExported
true
ethz.COinS
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