Role of NK cell subsets in organ-specific murine melanoma metastasis.

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 preferential...

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Main Authors: Zuhair K Ballas, Claire M Buchta, Timothy R Rosean, Jonathan W Heusel, Michael R Shey
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3679158?pdf=render
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spelling doaj-72f802d1b3f6426d8ad001bfc1ca63aa2020-11-24T21:34:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6559910.1371/journal.pone.0065599Role of NK cell subsets in organ-specific murine melanoma metastasis.Zuhair K BallasClaire M BuchtaTimothy R RoseanJonathan W HeuselMichael R SheyTumor 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.http://europepmc.org/articles/PMC3679158?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Zuhair K Ballas
Claire M Buchta
Timothy R Rosean
Jonathan W Heusel
Michael R Shey
spellingShingle Zuhair K Ballas
Claire M Buchta
Timothy R Rosean
Jonathan W Heusel
Michael R Shey
Role of NK cell subsets in organ-specific murine melanoma metastasis.
PLoS ONE
author_facet Zuhair K Ballas
Claire M Buchta
Timothy R Rosean
Jonathan W Heusel
Michael R Shey
author_sort Zuhair K Ballas
title Role of NK cell subsets in organ-specific murine melanoma metastasis.
title_short Role of NK cell subsets in organ-specific murine melanoma metastasis.
title_full Role of NK cell subsets in organ-specific murine melanoma metastasis.
title_fullStr Role of NK cell subsets in organ-specific murine melanoma metastasis.
title_full_unstemmed Role of NK cell subsets in organ-specific murine melanoma metastasis.
title_sort role of nk cell subsets in organ-specific murine melanoma metastasis.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2013-01-01
description 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.
url http://europepmc.org/articles/PMC3679158?pdf=render
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