Makoto Emori 1 , 2 , Tomohide Tsukahara 2 , * , Masaki Murase 1 , 2 , Masanobu Kano 1 , 2 , Kenji Murata 1 , 2 , Akari Takahashi 2 , Terufumi Kubo 2 , Hiroko Asanuma 3 , Kazuyo Yasuda 2 , Vitaly Kochin 2 , Mitsunori Kaya 1 , Satoshi Nagoya 1 , Jun Nishio 4 , Hiroshi Iwasaki 5 , Tomoko Sonoda 6 , Tadashi Hasegawa 3 , Toshihiko Torigoe 2 , Takuro Wada 1 , Toshihiko Yamashita 1 , Noriyuki Sato 2
20 December 2013
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.