神经营养因子Artemin在体内外促进胰腺腺癌的侵袭性和神经营养功能。
Neurotrophic Factor Artemin Promotes Invasiveness and Neurotrophic Function of Pancreatic Adenocarcinoma In Vivo and In Vitro.
作者信息
Gao Li, Bo Haiji, Wang Yang, Zhang Jing, Zhu Minghua
机构信息
From the *Department of Pathology, Changhai Hospital, Second Military Medical University; and †Department of Pathology, No. 455 Hospital, Shanghai, China.
出版信息
Pancreas. 2015 Jan;44(1):134-43. doi: 10.1097/MPA.0000000000000223.
OBJECTIVES
The aim of this study was to investigate the effect of the neurotrophic factor Artemin on neuroplasticity and perineural invasion of pancreatic adenocarcinoma.
METHODS
Artemin expressions were detected in human pancreatic adenocarcinoma tissues by Western blot and immunohistochemistry. Artemin overexpression and RNA interference in the pancreatic cancer cell lines were performed to evaluate the effects of Artemin on cell proliferation, invasion, and neurotrophic activity in vitro and in nude orthotopic transplantation tumor models.
RESULTS
Artemin expression in pancreatic cancer tissues was related to the incidence of lymphatic metastasis and perineural invasion as well as the mean density and total area of nerve fibers. Overexpression of Artemin in pancreatic cancer cell lines improved colony formation, cell migration, matrigel invasion, and neurotrophic activity in vitro. This overexpression also increased the volume of nude orthotopic transplantation tumors; promoted cancer cell invasion of the peripheral organs, nerves, vessels, and lymph nodes; and stimulated the proliferation of peritumoral nerve fibers. Artemin depletion by RNA interference had an inhibitory effect mentioned previously.
CONCLUSIONS
Artemin could promote invasiveness and neurotrophic function of pancreatic adenocarcinoma in vivo and in vitro. Therefore, Artemin could be used as a new therapeutic target of pancreatic carcinoma.
目的
本研究旨在探讨神经营养因子Artemin对胰腺腺癌神经可塑性和神经周围浸润的影响。
方法
采用蛋白质免疫印迹法和免疫组织化学法检测人胰腺腺癌组织中Artemin的表达。在胰腺癌细胞系中进行Artemin过表达和RNA干扰,以评估Artemin在体外和裸鼠原位移植瘤模型中对细胞增殖、侵袭及神经营养活性的影响。
结果
胰腺癌组织中Artemin的表达与淋巴转移和神经周围浸润的发生率以及神经纤维的平均密度和总面积有关。胰腺癌细胞系中Artemin的过表达改善了体外的集落形成、细胞迁移、基质胶侵袭及神经营养活性。这种过表达还增加了裸鼠原位移植瘤的体积;促进癌细胞向周围器官、神经、血管和淋巴结的侵袭;并刺激瘤周神经纤维的增殖。RNA干扰使Artemin表达降低产生了上述抑制作用。
结论
Artemin在体内和体外均可促进胰腺腺癌的侵袭性和神经营养功能。因此,Artemin可作为胰腺癌的一个新的治疗靶点。