Journal article
Role of NK cell subsets in organ-specific murine melanoma metastasis
PloS one, Vol.8(6), pp.e65599-e65599
2013
DOI: 10.1371/journal.pone.0065599
PMCID: PMC3679158
PMID: 23776508
Abstract
Tumor metastasis plays a major role in the morbidity and mortality of cancer patients. Among solid tumors that undergo metastasis, there is often a predilection to metastasize to a particular organ with, for example, prostate cancer preferentially metastasizing to bones and colon cancer preferentially metastasizing to the liver. Although many factors are thought to be important in establishing permissiveness for metastasis, the reasons for organ-specific predilection of each tumor are not understood. Using a B16 murine melanoma model, we tested the hypothesis that organ-specific NK cell subsets play a critical role in organ-specific metastasis of this tumor. Melanoma cells, given intravenously, readily colonized the lungs but not the liver. NK cell depletion (either iatrogenically or by using genetically targeted mice) resulted in substantial hepatic metastasis. Analysis of NK cell subsets, defined by the differential expression of a combination of CD27 and CD11b, indicated a significant difference in the distribution of NK cell subsets in the lung and liver with the mature subset being dominant in the lung and the immature subset being dominant in the liver. Several experimental approaches, including adoptive transfer, clearly indicated that the immature hepatic NK cell subset, CD27+ CD11b-, was protective against liver metastasis; this subset mediated its protection by a perforin-dependent cytotoxic mechanism. In contrast, the more mature NK cell subsets were more efficient at reducing pulmonary tumor load. These data indicate that organ-specific immune responses may play a pivotal role in determining the permissiveness of a given organ for the establishment of a metastatic niche.
Details
- Title: Subtitle
- Role of NK cell subsets in organ-specific murine melanoma metastasis
- Creators
- Zuhair K Ballas - Iowa City VA Medical Center and the Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America. ballasz@uiowa.eduClaire M BuchtaTimothy R RoseanJonathan W HeuselMichael R Shey
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.8(6), pp.e65599-e65599
- DOI
- 10.1371/journal.pone.0065599
- PMID
- 23776508
- PMCID
- PMC3679158
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science
- Grant note
- T32 AI007485 / NIAID NIH HHS
- Language
- English
- Date published
- 2013
- Academic Unit
- Immunology; Internal Medicine
- Record Identifier
- 9984094645202771
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