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Epigenetic and stem cell biomarkers in experimental melanoma metastases
Author(s) -
Lian Christine Guo,
Ma Jie,
Shi Yujiang Geno,
Zhan Qian,
Lezcano Cecilia,
Frank Markus H.,
Murphy George F.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.53.6
Subject(s) - vasculogenic mimicry , melanoma , stem cell , cancer research , epigenetics , cancer stem cell , lymph node , medicine , pathology , cancer , biology , metastasis , microbiology and biotechnology , biochemistry , gene
Little is know regarding epigenetic and cancer stem cell participation in melanoma metastases. We recently described two relevant biomarkers to address this issue, and herein utilize them to immunohistochemically evaluate metastases in the NSG murine‐human melanoma xenograft model. Subcutaneous xenografts derived from the C8161 cell line produced lymph node and lung, but rarely liver, metastases within four weeks. Metastases differed from primary xenografts by expressing increased immunoreactivity for the melanoma stem cell marker, ABCB5 ( Nature 2008), and selective loss from the ABCB5+ stem cell component of the epigenetic mark, 5‐hydroxymethyl cytosine (5‐hmC; Cell 2012). Reciprocal patterns of ABCB5 and 5‐hmC expression were prominent in lung metastases, which showed perivascular and peribronchial distributions, and in lymph node metastases, where vasculogenic mimicry‐like growth focally was documented. These data support the importance of cancer stem cells in the production and growth of melanoma metastases, and implicate loss of 5‐hmC as a potential epigenetic mediator of the metastatic stem cell phenotype. Study funded by NIH‐ GM078458 and NIH‐NCI 5P50CA093683–09.

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