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Characterization and Clinical Implication of Th1/Th2/Th17 Cytokines Produced from Three-Dimensionally Cultured Tumor Tissues Resected from Breast Cancer Patients
Authors:Anna Kiyomi  Masujiro Makita  Tomoko Ozeki  Na Li  Aiko Satomura  Sachiko Tanaka  Kenji Onda  Kentaro Sugiyama  Takuji Iwase  Toshihiko Hirano
Institution:Tokyo University of Pharmacy and Life Sciences, Department of Clinical Pharmacology, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan;The Cancer Institute Hospital of JFCR, Department of Breast Oncology, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan;Nippon Medical School Musashi Kosugi Hospital, Department of Breast Surgery, 1-396 Kosugimachi, Nakahara-ku, Kawasaki, Kanagawa 211-8533, Japan
Abstract:OBJECTIVES: Several cytokines secreted from breast cancer tissues are suggested to be related to disease prognosis. We examined Th1/Th2/Th17 cytokines produced from three-dimensionally cultured breast cancer tissues and related them with patient clinical profiles. METHODS: 21 tumor tissues and 9 normal tissues surgically resected from breast cancer patients were cultured in thermoreversible gelatin polymer–containing medium. Tissue growth and Th1/Th2/Th17 cytokine concentrations in the culture medium were analyzed and were related with hormone receptor expressions and patient clinical profiles. RESULTS: IL-6 and IL-10 were expressed highly in culture medium of both cancer and normal tissues. However, IFN-γ, TNF-α, IL-2, and IL-17A were not detected in the supernatant of the three-dimensionally cultured normal mammary gland and are seemed to be specific to breast cancer tissues. The growth abilities of hormone receptor–negative cancer tissues were significantly higher than those of receptor-positive tissues (P = 0.0383). Cancer tissues of stage ≥ IIB patients expressed significantly higher TNF-α levels as compared with those of patients with stage < IIB (P = 0.0096). CONCLUSIONS: The tumor tissues resected from breast cancer patients can grow in the three-dimensional thermoreversible gelatin polymer culture system and produce Th1/Th2/Th17 cytokines. Hormone receptor–positive cancer tissues showed less growth ability. TNF-α is suggested to be a biomarker for the cancer stage.
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