Department of Surgery, Trinity Centre for Health Sciences, Institute of Molecular Medicine, St James' Hospital, Trinity College Dublin, Ireland.
Clin Transl Oncol. 2012 Oct;14(10):774-82. doi: 10.1007/s12094-012-0863-6. Epub 2012 Aug 2.
The murine adipocyte cell line 3T3-L1 is well characterised and used widely, while the human pre-adipocyte cell strain, Simpson-Golabi-Behmel Syndrome (SGBS), requires validation for use in human studies. Obesity is currently estimated to account for up to 41 % of the worldwide cancer burden. A human in vitro model system is required to elucidate the molecular mechanisms for this poorly understood association. This work investigates the relevance of the SGBS cell strain for obesity and cancer research in humans.
Pre-adipocyte 3T3-L1 and SGBS were differentiated according to standard protocols. Morphology was assessed by Oil Red O staining. Adipocyte-specific gene expression was measured by qPCR and biochemical function was assessed by glycerol-3-phosphate dehydrogenase (GPDH) enzyme activity. Differential gene expression in oesophageal adenocarcinoma cell line OE33 following co-culture with SGBS or primary omental human adipocytes was investigated using Human Cancer Profiler qPCR arrays.
During the process of differentiation, SGBS expressed higher levels of adipocyte-specific transcripts and fully differentiated SGBS expressed more similar morphology, transcript levels and biochemical function to primary omental adipocytes, relative to 3T3-L1. Co-culture with SGBS or primary omental adipocytes induced differential expression of genes involved in adhesion (ITGB3), angiogenesis (IGF1, TEK, TNF, VEGFA), apoptosis (GZMA, TERT) and invasion and metastasis (MMP9, TIMP3) in OE33 tumour cells.
Comparable adipocyte-specific gene expression, biochemical function and a shared induced gene signature in co-cultured OE33 cells indicate that SGBS is a relevant in vitro model for obesity and cancer research in humans.
3T3-L1 是一种经过充分研究的小鼠脂肪细胞系，被广泛应用，而 Simpson-Golabi-Behmel 综合征（SGBS）人类前脂肪细胞株则需要在人类研究中得到验证。肥胖目前估计占全球癌症负担的 41%。需要建立人类体外模型系统来阐明这种尚未完全理解的关联的分子机制。这项工作研究了 SGBS 细胞株在肥胖和人类癌症研究中的相关性。
按照标准方案将前脂肪细胞 3T3-L1 和 SGBS 进行分化。通过油红 O 染色评估细胞形态。通过 qPCR 测量脂肪细胞特异性基因表达，通过甘油-3-磷酸脱氢酶（GPDH）酶活性评估生化功能。通过人类癌症分析 qPCR 阵列研究 SGBS 或原发性网膜人类脂肪细胞共培养后食管腺癌细胞系 OE33 中的差异基因表达。
在分化过程中，SGBS 表达更高水平的脂肪细胞特异性转录本，并且完全分化的 SGBS 表达的形态、转录本水平和生化功能与 3T3-L1 相比更类似于原发性网膜脂肪细胞。与 SGBS 或原发性网膜脂肪细胞共培养诱导了 OE33 肿瘤细胞中涉及粘附（ITGB3）、血管生成（IGF1、TEK、TNF、VEGFA）、凋亡（GZMA、TERT）和侵袭转移（MMP9、TIMP3）的基因的差异表达。
共培养的 OE33 细胞中相似的脂肪细胞特异性基因表达、生化功能和共享的诱导基因特征表明，SGBS 是肥胖和人类癌症研究的相关体外模型。
