High expression of CD109 antigen regulates the phenotype of cancer stem-like cells/cancer-initiating cells in the novel epithelioid sarcoma cell line ESX and is related to poor prognosis of soft tissue sarcoma

• Published in: PloS one Vol. 8; no. 12; p. e84187
• Main Authors: Emori, Makoto, Tsukahara, Tomohide, Murase, Masaki, Kano, Masanobu, Murata, Kenji, Takahashi, Akari, Kubo, Terufumi, Asanuma, Hiroko, Yasuda, Kazuyo, Kochin, Vitaly, Kaya, Mitsunori, Nagoya, Satoshi, Nishio, Jun, Iwasaki, Hiroshi, Sonoda, Tomoko, Hasegawa, Tadashi, Torigoe, Toshihiko, Wada, Takuro, Yamashita, Toshihiko, Sato, Noriyuki
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.12.2013; Public Library of Science (PLoS)
• Subjects: Adult; Amputation; Antigens; Antigens, CD - metabolism; Biomarkers; Bone surgery; Cancer; Cancer therapies; Cell culture; Cell Line, Tumor; Cell proliferation; Chemotherapy; Dehydrogenases; Disease control; DNA Primers - genetics; Ewings sarcoma; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - physiology; Genetic aspects; GPI-Linked Proteins - metabolism; Health aspects; Humans; Immunohistochemistry; Invasiveness; Isoenzymes - metabolism; Kaplan-Meier Estimate; Lymphatic system; Medical prognosis; Medical schools; Medicine; Melanoma; Metastasis; Musculoskeletal system; Neoplasm Proteins - metabolism; Neoplastic Stem Cells - cytology; Neoplastic Stem Cells - metabolism; Orthopedics; Pathology; Physicians; Polymerase Chain Reaction; Prognosis; Retinal Dehydrogenase - metabolism; RNA; RNA, Small Interfering - genetics; Sarcoma; Sarcoma - metabolism; Signal transduction; Skin cancer; Soft tissue sarcoma; Stem cells; Tissues; Tumor cell lines; Tumorigenicity; Tumors; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0084187

Epithelioid sarcoma (ES) is a relatively rare, highly malignant soft tissue sarcoma. The mainstay of treatment is resection or amputation. Currently other therapeutic options available for this disease are limited. Therefore, a novel therapeutic option needs to be developed. In the present study, we established a new human ES cell line (ESX) and analyzed the characteristics of its cancer stem-like cells/cancer-initiating cells (CSCs/CICs) based on ALDH1 activity. We demonstrated that a subpopulation of ESX cells with high ALDH1 activity (ALDH(high) cells) correlated with enhanced clonogenic ability, sphere-formation ability, and invasiveness in vitro and showed higher tumorigenicity in vivo. Next, using gene expression profiling, we identified CD109, a GPI-anchored protein upregulated in the ALDH(high) cells. CD109 mRNA was highly expressed in various sarcoma cell lines, but weakly expressed in normal adult tissues. CD109-positive cells in ESX predominantly formed spheres in culture, whereas siCD109 reduced ALDH1 expression and inhibited the cell proliferation in vitro. Subsequently, we evaluated the expression of CD109 protein in 80 clinical specimens of soft tissue sarcoma. We found a strong correlation between CD109 protein expression and the prognosis (P = 0.009). In conclusion, CD109 might be a CSC/CIC marker in epithelioid sarcoma. Moreover, CD109 is a promising prognostic biomarker and a molecular target of cancer therapy for sarcomas including ES.