Zhang Hao, Ren Yuan, Pang Deyan, Liu Caigang
Department of Breast Surgery, Second hospital of Dalian Medical University, Zhongshan Road, Dalian 116023, People's Republic of China.
World J Surg Oncol. 2014 May 7;12:142. doi: 10.1186/1477-7819-12-142.
We investigated the expression status of AGBL2 and its inhibitor latexin in breast cancer stem cells and its clinical implications in order to lay a foundation for managing breast cancer.
CD44+/CD24- tumor cells (CSC) from clinical specimens were sorted using flow cytometry. AGBL2 expression status was detected in CSC and 126 breast cancer specimens by western blot and immunohistochemistry staining. The relationship between the AGBL2 protein and clinicopathological parameters and prognosis was subsequently determined.
As a result, CSC are more likely to generate new tumors in mice and cell microspheres that are deficient in non-obese diabetic/severe combined immunodeficiency mice (NOD/SCID) compared to the control group. The AGBL2 protein was expressed higher in CSC induced to epithelial to mesenchymal transition (EMT) when compared to the control cells, and was found to be related to CSC chemotherapy resistance. After Spearman regression correlation analysis, AGBL2 was observed to be related to clinical stage, histological stage, and lymph node metastasis. In the Cox regression test, the AGBL2 protein was detected as an independent prognostic factor. Through immunoprecipitation, AGBL2 and latexin could form immune complexes.
These results demonstrate that AGBL2 is a latexin-interacting protein that regulates the tubulin tyrosination cycle and is a potential target for intervention.
我们研究了AGBL2及其抑制剂latexin在乳腺癌干细胞中的表达状况及其临床意义,以便为乳腺癌的治疗奠定基础。
使用流式细胞术对临床标本中的CD44+/CD24-肿瘤细胞(癌症干细胞)进行分选。通过蛋白质免疫印迹法和免疫组织化学染色检测癌症干细胞和126例乳腺癌标本中AGBL2的表达状况。随后确定AGBL2蛋白与临床病理参数及预后之间的关系。
结果显示,与对照组相比,癌症干细胞在非肥胖糖尿病/重症联合免疫缺陷小鼠(NOD/SCID)体内及细胞微球中更易产生新肿瘤。与对照细胞相比,在诱导上皮-间质转化(EMT)的癌症干细胞中AGBL2蛋白表达更高,且发现其与癌症干细胞的化疗耐药性有关。经Spearman回归相关性分析后,观察到AGBL2与临床分期、组织学分级及淋巴结转移有关。在Cox回归检验中,AGBL2蛋白被检测为独立的预后因素。通过免疫沉淀发现,AGBL2和latexin可形成免疫复合物。
这些结果表明,AGBL2是一种与latexin相互作用的蛋白,可调节微管蛋白酪氨酸化循环,是一个潜在的干预靶点。