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

Makoto Emori,Kenji Murata,Tadashi Hasegawa,Masanobu Kano,Takuro Wada,Satoshi Nagoya,Tomoko Sonoda,Hiroko Asanuma,Vitaly Kochin,Jun Nishio,Kazuyo Yasuda,Toshihiko Yamashita,Toshihiko Torigoe,Mitsunori Kaya,Masaki Murase,Tomohide Tsukahara,Noriyuki Sato,Terufumi Kubo,Hiroshi Iwasaki,Akiko Takahashi

doi:10.1371/journal.pone.0084187

Makoto Emori, Kenji Murata + Show 18 more

Open Access

https://doi.org/10.1371/journal.pone.0084187

Copy DOI

Journal: PloS one	Publication Date: Dec 20, 2013
Citations: 56	License type: CC BY 4.0

Affiliation: Sapporo Medical University, Fukuoka University

Abstract

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 (ALDHhigh 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 ALDHhigh 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.

Highlights

Epithelioid sarcoma (ES) is a relatively rare and highly malignant soft tissue sarcoma (STS) accounting for
aldehyde dehydrogenase 1 (ALDH1) activity was used, either alone or in combination with cell surface markers, to identify cancer stem-like cells (CSCs)/cancer initiating cells (CICs) in hematologic malignancies and carcinomas derived from the lung and prostate [6,7,8]
Immunostaining analysis of the xenografted tumors revealed a staining pattern similar to that of the ESX cells (Figure 1C) and the original tumor (Figure S1C). These findings indicated that the established cell line was consistent with the profile of the original tumor