Expression of CD133 and other putative stem cell markers in uveal melanoma.
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Expression of CD133 and other putative stem cell markers in uveal melanoma. / Berna-Thill, Michelle; Berna, Marc; Grierson, Rebecca; Reinhart, Inna; Voelkel, Tobias; Piechaczek, Christoph; Galambos, Peter; Jager, Martine J; Richard, Gisbert; Lange, Claudia; Gehling, Ursula.
In: MELANOMA RES, Vol. 21, No. 5, 5, 2011, p. 405-416.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Expression of CD133 and other putative stem cell markers in uveal melanoma.
AU - Berna-Thill, Michelle
AU - Berna, Marc
AU - Grierson, Rebecca
AU - Reinhart, Inna
AU - Voelkel, Tobias
AU - Piechaczek, Christoph
AU - Galambos, Peter
AU - Jager, Martine J
AU - Richard, Gisbert
AU - Lange, Claudia
AU - Gehling, Ursula
PY - 2011
Y1 - 2011
N2 - 'Cancer stem cells' (CSCs) are tumor cells with stem cell properties hypothesized to be responsible for tumorigenesis, metastatis, and resistance to treatment, and have been identified in different tumors including cutaneous melanoma, using stem cell markers such as CD133. This study explored expression of CD133 and other putative stem cell markers in uveal melanoma. Eight uveal melanoma cell lines were subjected to flow-cytometric (fluorescence-activated cell sorting) analysis of CD133 and other stem cell markers. Eight paraffin-embedded tumors were analyzed by immunohistochemistry for CD133, Pax6, Musashi, nestin, Sox2, ABCB5, and CD68 expressions. Ocular, uveal melanoma, and hematopoietic stem cell distributions of C-terminal and N-terminal CD133 mRNA splice variants were compared by reverse-transcription PCR. Fluorescence-activated cell sorting analysis revealed a population of CD133-positive/nestin-positive cells in cell lines Mel270, OMM 2.3, and OMM2.5. All cell lines studied were positive for nestin, CXCR-4, CD44, and c-kit. Immunohistochemistry identified cells positive for CD133, Pax6, Musashi, nestin, Sox2, ABCB5, and CD68 predominantly at the invading tumor front. C-terminal primers interacting with CD133 splice variant s2 detected a novel variant lacking exon 27. Differential expression of CD133 splice variants was found in iris, ciliary body, retina, and retinal pigment epithelium/choroid as well as in uveal melanoma cell lines. mRNA for nestin, Sox2, and Musashi was present in all studied cell lines. Uveal melanoma such as cutaneous melanoma may therefore contain CSCs. Further experiments are needed to isolate stem cell marker-positive cells, to evaluate their functional properties and to explore therapeutical approaches to these putative CSCs in uveal melanoma.
AB - 'Cancer stem cells' (CSCs) are tumor cells with stem cell properties hypothesized to be responsible for tumorigenesis, metastatis, and resistance to treatment, and have been identified in different tumors including cutaneous melanoma, using stem cell markers such as CD133. This study explored expression of CD133 and other putative stem cell markers in uveal melanoma. Eight uveal melanoma cell lines were subjected to flow-cytometric (fluorescence-activated cell sorting) analysis of CD133 and other stem cell markers. Eight paraffin-embedded tumors were analyzed by immunohistochemistry for CD133, Pax6, Musashi, nestin, Sox2, ABCB5, and CD68 expressions. Ocular, uveal melanoma, and hematopoietic stem cell distributions of C-terminal and N-terminal CD133 mRNA splice variants were compared by reverse-transcription PCR. Fluorescence-activated cell sorting analysis revealed a population of CD133-positive/nestin-positive cells in cell lines Mel270, OMM 2.3, and OMM2.5. All cell lines studied were positive for nestin, CXCR-4, CD44, and c-kit. Immunohistochemistry identified cells positive for CD133, Pax6, Musashi, nestin, Sox2, ABCB5, and CD68 predominantly at the invading tumor front. C-terminal primers interacting with CD133 splice variant s2 detected a novel variant lacking exon 27. Differential expression of CD133 splice variants was found in iris, ciliary body, retina, and retinal pigment epithelium/choroid as well as in uveal melanoma cell lines. mRNA for nestin, Sox2, and Musashi was present in all studied cell lines. Uveal melanoma such as cutaneous melanoma may therefore contain CSCs. Further experiments are needed to isolate stem cell marker-positive cells, to evaluate their functional properties and to explore therapeutical approaches to these putative CSCs in uveal melanoma.
KW - Adult
KW - Animals
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Aged, 80 and over
KW - Immunohistochemistry
KW - Mice
KW - Antigens, CD/biosynthesis/genetics
KW - Glycoproteins/biosynthesis/genetics
KW - Intermediate Filament Proteins/biosynthesis
KW - Melanoma/genetics/metabolism/pathology
KW - Neoplastic Stem Cells/metabolism/pathology
KW - Nerve Tissue Proteins/biosynthesis
KW - Peptides/genetics
KW - RNA, Messenger/biosynthesis/genetics
KW - Tumor Markers, Biological/biosynthesis/genetics
KW - Uveal Neoplasms/genetics/metabolism/pathology
KW - Adult
KW - Animals
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Aged, 80 and over
KW - Immunohistochemistry
KW - Mice
KW - Antigens, CD/biosynthesis/genetics
KW - Glycoproteins/biosynthesis/genetics
KW - Intermediate Filament Proteins/biosynthesis
KW - Melanoma/genetics/metabolism/pathology
KW - Neoplastic Stem Cells/metabolism/pathology
KW - Nerve Tissue Proteins/biosynthesis
KW - Peptides/genetics
KW - RNA, Messenger/biosynthesis/genetics
KW - Tumor Markers, Biological/biosynthesis/genetics
KW - Uveal Neoplasms/genetics/metabolism/pathology
M3 - SCORING: Journal article
VL - 21
SP - 405
EP - 416
JO - MELANOMA RES
JF - MELANOMA RES
SN - 0960-8931
IS - 5
M1 - 5
ER -