Biomarkers of residual disease, disseminated tumor cells, and metastases in the MMTV-PyMT breast cancer model.

Cancer metastases arise in part from disseminated tumor cells originating from the primary tumor and from residual disease persisting after therapy. The identification of biomarkers on micro-metastases, disseminated tumors, and residual disease may yield novel tools for early detection and treatment...

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Autores principales:	Christian Franci, Jenny Zhou, Zhaoshi Jiang, Zora Modrusan, Zinaida Good, Erica Jackson, Hosein Kouros-Mehr
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/82ac3cf886084e00ac9dd826fcb44bab
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spelling	oai:doaj.org-article:82ac3cf886084e00ac9dd826fcb44bab2021-11-18T07:54:11ZBiomarkers of residual disease, disseminated tumor cells, and metastases in the MMTV-PyMT breast cancer model.1932-620310.1371/journal.pone.0058183https://doaj.org/article/82ac3cf886084e00ac9dd826fcb44bab2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23520493/?tool=EBIhttps://doaj.org/toc/1932-6203Cancer metastases arise in part from disseminated tumor cells originating from the primary tumor and from residual disease persisting after therapy. The identification of biomarkers on micro-metastases, disseminated tumors, and residual disease may yield novel tools for early detection and treatment of these disease states prior to their development into metastases and recurrent tumors. Here we describe the molecular profiling of disseminated tumor cells in lungs, lung metastases, and residual tumor cells in the MMTV-PyMT breast cancer model. MMTV-PyMT mice were bred with actin-GFP mice, and focal hyperplastic lesions from pubertal MMTV-PyMT;actin-GFP mice were orthotopically transplanted into FVB/n mice to track single tumor foci. Tumor-bearing mice were treated with TAC chemotherapy (docetaxel, doxorubicin, cyclophosphamide), and residual and relapsed tumor cells were sorted and profiled by mRNA microarray analysis. Data analysis revealed enrichment of the Jak/Stat pathway, Notch pathway, and epigenetic regulators in residual tumors. Stat1 was significantly up-regulated in a DNA-damage-resistant population of residual tumor cells, and a pre-existing Stat1 sub-population was identified in untreated tumors. Tumor cells from adenomas, carcinomas, lung disseminated tumor cells, and lung metastases were also sorted from MMTV-PyMT transplant mice and profiled by mRNA microarray. Whereas disseminated tumors cells appeared similar to carcinoma cells at the mRNA level, lung metastases were genotypically very different from disseminated cells and primary tumors. Lung metastases were enriched for a number of chromatin-modifying genes and stem cell-associated genes. Histone analysis of H3K4 and H3K9 suggested that lung metastases had been reprogrammed during malignant progression. These data identify novel biomarkers of residual tumor cells and disseminated tumor cells and implicate pathways that may mediate metastasis formation and tumor relapse after therapy.Christian FranciJenny ZhouZhaoshi JiangZora ModrusanZinaida GoodErica JacksonHosein Kouros-MehrPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e58183 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christian Franci Jenny Zhou Zhaoshi Jiang Zora Modrusan Zinaida Good Erica Jackson Hosein Kouros-Mehr Biomarkers of residual disease, disseminated tumor cells, and metastases in the MMTV-PyMT breast cancer model.
description	Cancer metastases arise in part from disseminated tumor cells originating from the primary tumor and from residual disease persisting after therapy. The identification of biomarkers on micro-metastases, disseminated tumors, and residual disease may yield novel tools for early detection and treatment of these disease states prior to their development into metastases and recurrent tumors. Here we describe the molecular profiling of disseminated tumor cells in lungs, lung metastases, and residual tumor cells in the MMTV-PyMT breast cancer model. MMTV-PyMT mice were bred with actin-GFP mice, and focal hyperplastic lesions from pubertal MMTV-PyMT;actin-GFP mice were orthotopically transplanted into FVB/n mice to track single tumor foci. Tumor-bearing mice were treated with TAC chemotherapy (docetaxel, doxorubicin, cyclophosphamide), and residual and relapsed tumor cells were sorted and profiled by mRNA microarray analysis. Data analysis revealed enrichment of the Jak/Stat pathway, Notch pathway, and epigenetic regulators in residual tumors. Stat1 was significantly up-regulated in a DNA-damage-resistant population of residual tumor cells, and a pre-existing Stat1 sub-population was identified in untreated tumors. Tumor cells from adenomas, carcinomas, lung disseminated tumor cells, and lung metastases were also sorted from MMTV-PyMT transplant mice and profiled by mRNA microarray. Whereas disseminated tumors cells appeared similar to carcinoma cells at the mRNA level, lung metastases were genotypically very different from disseminated cells and primary tumors. Lung metastases were enriched for a number of chromatin-modifying genes and stem cell-associated genes. Histone analysis of H3K4 and H3K9 suggested that lung metastases had been reprogrammed during malignant progression. These data identify novel biomarkers of residual tumor cells and disseminated tumor cells and implicate pathways that may mediate metastasis formation and tumor relapse after therapy.
format	article
author	Christian Franci Jenny Zhou Zhaoshi Jiang Zora Modrusan Zinaida Good Erica Jackson Hosein Kouros-Mehr
author_facet	Christian Franci Jenny Zhou Zhaoshi Jiang Zora Modrusan Zinaida Good Erica Jackson Hosein Kouros-Mehr
author_sort	Christian Franci
title	Biomarkers of residual disease, disseminated tumor cells, and metastases in the MMTV-PyMT breast cancer model.
title_short	Biomarkers of residual disease, disseminated tumor cells, and metastases in the MMTV-PyMT breast cancer model.
title_full	Biomarkers of residual disease, disseminated tumor cells, and metastases in the MMTV-PyMT breast cancer model.
title_fullStr	Biomarkers of residual disease, disseminated tumor cells, and metastases in the MMTV-PyMT breast cancer model.
title_full_unstemmed	Biomarkers of residual disease, disseminated tumor cells, and metastases in the MMTV-PyMT breast cancer model.
title_sort	biomarkers of residual disease, disseminated tumor cells, and metastases in the mmtv-pymt breast cancer model.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/82ac3cf886084e00ac9dd826fcb44bab
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Biomarkers of residual disease, disseminated tumor cells, and metastases in the MMTV-PyMT breast cancer model.

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