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人高钙血症型卵巢小细胞癌细胞系(OS-1)的建立与鉴定,该细胞系分泌甲状旁腺激素(PTH)、甲状旁腺激素相关蛋白(PthrP)和促肾上腺皮质激素(ACTH)——特别提及抗癌药物的敏感性

Establishment and characterization of a human ovarian small cell carcinoma, hypercalcemic type, cell line (OS-1) secreting PTH, PthrP and ACTH--special reference to the susceptibility of anti-cancer drugs.

作者信息

Ohi Satoshi, Niimi Shigeki, Okada Naoya, Yamada Kyosuke, Tachibana Toshiaki, Hashimoto Hisashi, Nakajima Masako, Yasuda Mitsuru, Tanaka Tadao, Sato Kahei, Ishikawa Hiroshi

机构信息

Department of Anatomy II, Jikei University of Medicine.

出版信息

Hum Cell. 2004 Dec;17(4):203-9. doi: 10.1111/j.1749-0774.2004.tb00044.x.

Abstract

We successfully established a novel cell line (OS-1) derived from human ovarian small cell carcinoma, hypercalcemic type secreted PTH, PTH-rP and ACTH. The OS-1 cell line was established from metastatic focus of uterus. A patient was 25-year-old Japanese woman. The first she received left ovariectomy on April 2002. The histopathological diagnosis was ovarian small cell carcinoma, pT2c, Nx, Mx. Then on June 2003, metastatic focus of uterus was ectomied. A part of the recurrent tumor of uterus was cut into small pieces with razor blades, and dissociated with 0.1% trypsin-0.02% EDTA/ PBS(-) solution at room temperature. The single cells and small cell clusters were seeded into 60mm dishes and cultured in growth medium (GM: DMEM/F12 supplemented with 20% fetal bovine serum and 0.1% non-essential amino acids solution) at 37 degrees C, 4.7% CO2 in humidified air. Medium was exchanged twice a week. The OS-1 cells grew as floating cultures in the dishes. Radioimmunoassay of the conditioned media was revealed that the cultures secreted large amount of PTH, PTHrP and ACTH simultaneously. Susceptibilities of anti-cancer drugs to the OS-1 cells were examined using oxygen electrode meter (Daikin), and the results suggested VLB and TXL were effective, and CDDP, CPT-11, VP-16, VCR, CPA, MMC and CBDCA were not effective. In our knowledge, it is the first report that the cell line secreting PTH, PTHrP and ACTH was successfully established from ovarian small cell carcinoma, hypercalcemic type. We expect that OS-1 cell line contribute to study on the mechanism of ectopic hormone secretion and susceptibility of anti cancer drugs to the small cell carcinoma.

摘要

我们成功建立了一种源自人高钙血症型卵巢小细胞癌的新型细胞系(OS-1),其可分泌甲状旁腺激素(PTH)、甲状旁腺激素相关蛋白(PTH-rP)和促肾上腺皮质激素(ACTH)。OS-1细胞系是从子宫转移灶建立的。患者为一名25岁的日本女性。她于2002年4月首次接受左侧卵巢切除术。组织病理学诊断为卵巢小细胞癌,pT2c,Nx,Mx。然后在2003年6月,切除子宫转移灶。用剃须刀片将子宫复发性肿瘤的一部分切成小块,在室温下用0.1%胰蛋白酶-0.02%乙二胺四乙酸/无钙镁磷酸盐缓冲液(PBS(-))溶液解离。将单细胞和小细胞团接种到60mm培养皿中,在生长培养基(GM:添加20%胎牛血清和0.1%非必需氨基酸溶液的DMEM/F12)中于37℃、4.7%二氧化碳的湿润空气中培养。每周更换两次培养基。OS-1细胞在培养皿中呈悬浮培养生长。对条件培养基的放射免疫分析显示,培养物同时分泌大量的PTH、PTHrP和ACTH。使用氧电极仪(大金)检测抗癌药物对OS-1细胞的敏感性,结果表明长春碱(VLB)和紫杉醇(TXL)有效,而顺铂(CDDP)、伊立替康(CPT-11)、依托泊苷(VP-16)、长春新碱(VCR)、环磷酰胺(CPA)、丝裂霉素(MMC)和卡铂(CBDCA)无效。据我们所知,这是首次报道从高钙血症型卵巢小细胞癌成功建立分泌PTH、PTHrP和ACTH的细胞系。我们期望OS-1细胞系有助于研究异位激素分泌机制以及抗癌药物对小细胞癌的敏感性。

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