Takuma Hayashi1, Kenji Sano2, Tomoyuki Ichimura3, Yae Kanai4, Dorit Zharhary5, Hiroyuki Aburatani6, Nobuo Yaegashi7, Ikuo Konishi8. 1. Department of Molecular and Cellular Immunology, Shinshu University Graduate School of Medicine, Nagano, Japan yoyoyo224@hotmail.com. 2. Department of Medical Laboratory, Shinshu University Hospital, Nagano, Japan. 3. Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine, Osaka, Japan. 4. Department of Pathology, Keio University School of Medicine, Tokyo, Japan. 5. SIGMA-Aldrich Israel, Rehovot, Israel. 6. RCAST, The University of Tokyo, Tokyo, Japan. 7. Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Miyagi, Japan. 8. National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
Abstract
BACKGROUND/AIM: Uterine leiomyosarcoma (Ut-LMS) is a refractory tumor that repeatedly recurs with hematogenous metastasis, which may be due to the presence of drug-resistant tumor stem cells. Its treatment is limited to surgical procedures. We previously reported that Ut-LMS spontaneously developed in mice deficient in the proteasome component low-molecular mass polypeptide 2 (LMP2). We showed that LMP2 expression was significantly attenuated specifically in human Ut-LMS. The aim of this study was to investigate the role of LMP2 in hematogenous metastasis using xenograft models with tumor stem-like cells. MATERIALS AND METHODS: We isolated tumor stem-like cells from LMP2-negative primary human Ut-LMS cells established from a human Ut-LMS tissue using the side population (SP) procedure. These cells were used to develop xenograft models with tumor stem-like cells. RESULTS: Human Ut-LMS stem-like cells showed stronger hematogenous metastatic potential than normal Ut-LMS cells. Tumor stem-like cells also had the potential to differentiate into vascular endothelial cells through VEGF-A signaling. CONCLUSION: These results reflect frequent hematogenous metastasis by human Ut-LMS in clinical settings, and may lead to the development of treatments that inhibit hematogenous metastasis in Ut-LMS. Copyright
BACKGROUND/AIM: Uterine leiomyosarcoma (Ut-LMS) is a refractory tumor that repeatedly recurs with hematogenous metastasis, which may be due to the presence of drug-resistant tumor stem cells. Its treatment is limited to surgical procedures. We previously reported that Ut-LMS spontaneously developed in mice deficient in the proteasome component low-molecular mass polypeptide 2 (LMP2). We showed that LMP2 expression was significantly attenuated specifically in human Ut-LMS. The aim of this study was to investigate the role of LMP2 in hematogenous metastasis using xenograft models with tumor stem-like cells. MATERIALS AND METHODS: We isolated tumor stem-like cells from LMP2-negative primary human Ut-LMS cells established from a human Ut-LMS tissue using the side population (SP) procedure. These cells were used to develop xenograft models with tumor stem-like cells. RESULTS:Human Ut-LMS stem-like cells showed stronger hematogenous metastatic potential than normal Ut-LMS cells. Tumor stem-like cells also had the potential to differentiate into vascular endothelial cells through VEGF-A signaling. CONCLUSION: These results reflect frequent hematogenous metastasis by human Ut-LMS in clinical settings, and may lead to the development of treatments that inhibit hematogenous metastasis in Ut-LMS. Copyright