CD146 is a novel marker for highly tumorigenic cells and a potential therapeutic target in malignant rhabdoid tumor

Malignant rhabdoid tumor (MRT) is a rare, highly aggressive pediatric malignancy that primarily develops during infancy and early childhood. Despite the existing standard of intensive multimodal therapy, the prognosis of patients with MRT is dismal; therefore, a greater understanding of the biology...

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Bibliographic Details
Published in:	Oncogene Vol. 35; no. 40; pp. 5317 - 5327
Main Authors:	Nodomi, S, Umeda, K, Saida, S, Kinehara, T, Hamabata, T, Daifu, T, Kato, I, Hiramatsu, H, Watanabe, K-i, Kuwahara, Y, Iehara, T, Adachi, S, Konishi, E, Nakahata, T, Hosoi, H, Heike, T
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 06-10-2016 Nature Publishing Group
Subjects:	13/1 13/2 13/31 13/51 13/89 631/67/1059/602 631/67/2332 Adolescent Adult Aged Analysis Animals Antibodies Apoptosis Apoptosis - genetics Biomarkers Biomarkers, Tumor - biosynthesis Biomarkers, Tumor - genetics Cancer Carcinogenesis - genetics CD146 Antigen - biosynthesis CD146 Antigen - genetics Cell Biology Cell Lineage - genetics Child Child, Preschool Female Gene Expression Regulation, Neoplastic - genetics Human Genetics Humans Internal Medicine Male Medical care quality Medical prognosis Medicine Medicine & Public Health Melanoma Mice Middle Aged Neural Crest - pathology Oncology Original original-article Pediatrics Prognosis Rhabdoid Tumor - genetics Rhabdoid Tumor - pathology Rhabdoid Tumor - therapy Tumors Xenograft Model Antitumor Assays
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Summary:	Malignant rhabdoid tumor (MRT) is a rare, highly aggressive pediatric malignancy that primarily develops during infancy and early childhood. Despite the existing standard of intensive multimodal therapy, the prognosis of patients with MRT is dismal; therefore, a greater understanding of the biology of this disease is required to establish novel therapies. In this study, we identified a highly tumorigenic sub-population in MRT, based on the expression of CD146 (also known as melanoma cell adhesion molecule), a cell adhesion molecule expressed by neural crest cells and various derivatives. CD146 + cells isolated from four MRT cell lines by cell sorting exhibited enhanced self-renewal and invasive potential in vitro . In a xenograft model using immunodeficient NOD/Shi-scid IL-2Rγ-null mice, purified CD146 + cells obtained from MRT cell lines or a primary tumor exhibited the exclusive ability to form tumors in vivo . Blocking of CD146-related mechanisms, either by short hairpin RNA knockdown or treatment with a polyclonal antibody against CD146, effectively suppressed tumor growth of MRT cells both in vitro and in vivo via induction of apoptosis by inactivating Akt. Furthermore, CD146 positivity in immunohistological analysis of 11 MRT patient samples was associated with poor patient outcomes. These results suggest that CD146 defines a distinct sub-population in MRT with high tumorigenic capacity and that this marker represents a promising therapeutic target.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0950-9232 1476-5594
DOI:	10.1038/onc.2016.72