ASPS-1, a novel cell line manifesting key features of alveolar soft part sarcoma.
ASPS-1, a novel cell line manifesting key features of alveolar soft part sarcoma.
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DOI：
10.1097/mph.0b013e3182002f9f
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发表时间：
2011-07
期刊：
影响因子：
--
通讯作者：
Shoemaker RH
中科院分区：
文献类型：
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作者：
Kenney S;Vistica DT;Stockwin LH;Burkett S;Hollingshead MG;Borgel SD;Butcher DO;Schrump DS;Shoemaker RH
本文报道了肺泡状软组织肉瘤(ASPS)的体外生长及ASPS-1细胞系的建立。利用新近建立的淋巴结转移的ASPS异种移植模型，通过70μm滤膜捕获ASPS异种移植瘤，从ASPS异种移植瘤中分离出由15~25个ASPS细胞组成的器官巢，并进行体外培养。在附着于底物后，这些巢沉积了ASPS细胞的小聚体。这些细胞生长缓慢，经过3年的扩增，保持了与患者原始ASPS肿瘤和异种移植瘤一致的特征，包括：(1)存在肺泡软部分基因位点-转录因子E3型融合转录本和核表达；(2)维持ASPS的t(X；17)(p11；q25)易位特征；血管生成(ANGPTL2、HIF-1-α、MDK、c-MET、血管内皮生长因子、TIMP-2)、细胞增殖(PR1、PCSK1)、转移(ADAM9)、转录因子BHLHB3、肌肉特异性转录产物TRIM63和ITGβ1BP3的表达上调。该ASPS细胞系在软琼脂中形成集落，并在NOD.SCID/NCR小鼠中保留了产生高度血管化的ASPS肿瘤的能力。免疫组织化学显示这些肿瘤上的ASPS标志物与原始患者肿瘤的相似，也与移植的ASPS肿瘤相似。我们预计，该ASPS细胞系将加速对ASPS生物学的研究，包括识别治疗这种生长缓慢的软组织肉瘤的新治疗方法。
In vitro growth of alveolar soft part sarcoma (ASPS) and establishment of an ASPS cell line, ASPS-1, are described in this study. Using a recently developed xenograft model of ASPS derived from a lymph node metastasis, organoid nests consisting of 15 to 25 ASPS cells were isolated from ASPS xenograft tumors by capture on 70 μm filters and plated in vitro. After attachment to the substratum, these nests deposited small aggregates of ASPS cells. These cells grew slowly and were expanded over a period of 3 years and have maintained characteristics consistent with those of both the original ASPS tumor from the patient and the xenograft tumor including (1) presence of the alveolar soft part locus-transcription factor E3 type 1 fusion transcript and nuclear expression of the alveolar soft part locus-transcription factor E3 type 1 fusion protein; (2) maintenance of the t(X;17)(p11;q25) translocation characteristic of ASPS; and (3) expression of upregulated ASPS transcripts involved in angiogenesis (ANGPTL2, HIF-1-α, MDK, c-MET, VEGF, and TIMP-2), cell proliferation (PRL, PCSK1), metastasis (ADAM9), as well as the transcription factor BHLHB3 and the muscle-specific transcripts TRIM63 and ITGβ1BP3. This ASPS cell line forms colonies in soft agar and retains the ability to produce highly vascularized ASPS tumors in NOD.SCID/NCr mice. Immunohistochemistry of selected ASPS markers on these tumors indicated similarity to those of the original patient tumor as well as to the xenografted ASPS tumor. We anticipate that this ASPS cell line will accelerate investigations into the biology of ASPS including identification of new therapeutic approaches for treatment of this slow growing soft tissue sarcoma.