E-cad在低位直肠癌淋巴结转移裸鼠模型血清及移植瘤中的表达及其意义

目的探讨裸鼠低位直肠癌淋巴结转移模型血清及移植瘤组织中E-钙黏蛋白(E-cad)的表达情况,分析其在直肠癌淋巴结转移过程中的作用。方法取对数生长期的人大肠癌细胞株SW480接种于裸鼠直肠黏膜下,建立裸鼠低位直肠癌淋巴结转移模型。120只裸鼠随机分为3组,每组40只,A组(直肠癌模型组)采用二甲基肼注射+SW480种植,B组(二甲基肼对照组)采用二甲基肼注射,C组(空白对照组)不作任何处理。采用ELISA检测血清E-cad的含量,采用Western blot法、RT-PCR法检测种植瘤组织中E-cad蛋白及mRNA表达水平。结果A组裸鼠的血清E-Cad含量为(19.48±1.25)mg/L,明显高于B组裸鼠和C组裸鼠的血清E-Cad含量(2.36±0.18mg/L和2.15±0.12 mg/L)(t=8.28,9.01,P0.05)。发现侧方淋巴结转移的裸鼠血清E-Cad含量,明显高于未发现侧方淋巴结转移的裸鼠,差异有显著性(t=10.28,P0.05)。A组裸鼠移植瘤组织中E-Cad蛋白的表达强度弱于B组和C组(t=9.81,7.69,P0.05)。A组中,有侧方淋巴结转移发生的裸鼠移植瘤组织中E-Cad蛋白表达强度较未有侧方淋巴结转移发生的裸鼠移植瘤组织中表达明显减弱,差异有显著性(t=9.36,P0.05)。A组裸鼠移植瘤组织中E-Cad mRNA表达明显下调,与B组和C组比较,有明显的差异(P0.05)。A组中发现侧方淋巴结转移的裸鼠移植瘤组织中E-Cad mRNA表达强度明显下调,与未发现侧方淋巴结转移的裸鼠比较,差异有显著性(t=7.85,P0.05)。结论血清E-cad的表达水平可能与直肠癌淋巴转移密切相关,同时直肠癌组织中E-Cad蛋白和mRNA表达减弱或缺失,导致癌细胞间粘附性降低,促进癌细胞获得侵袭和转移的能力。

Expression and significance of E-cadherin in the serum and transplanted tumor of nude mouse model of low rectal cancer with lymph node metastasis

Objective To establish a nude mouse model of low rectal cancer with lymph node metastasis, to detect the expression of E-calcium (E-cad) in the serum and transplanted tumor tissue of the mice, and to analyze the role of E-cad in lymph node metastasis of rectal cancer. Methods Human colorectal adenocarcinoma cells (SW-480) were inoculated into the rectal submucosa of nude mice to establish a model of low rectal cancer with lymph node metastasis. 120 nude mice were randomly divided into three groups (40 mice in each group). Group A (rectal cancer model group) was injected with dimethylhydrazine and implanted with SW480 cells. Group B (dimethylhydrazine control group) was injected with dimethylhydrazine alone. The group C (control group) received no treatment. Serum E-cad was detected by ELISA. The mRNA and protein expression of E-cad in the tumor tissue was detected by RT-PCR and western blot, respectively. Results The serum level of E-cad in group A was 19.48±1.25 mg/L, significantly higher than those in groups B (2.36±0.18 mg/L) and C (2.15±0.12 mg/L) (t=8.28, 9.01, P< 0.05). The serum levels of E-cad were significantly higher in the nude mice with lateral lymph node metastasis than those without lymph node metastasis (t=10.28, P< 0.05). The protein expression of E-cad in the group A was lower than that in the groups B and C (t=9.81, 7.69, P< 0.05). In the group A, the protein expression of E-cad in the nude mice with lateral lymph node metastasis was significantly lower than that without lateral lymph node metastasis (t=9.36, P< 0.05). The mRNA expression of E-cad in the group A was significantly lower than that in the groups B and C (P< 0.05), and the mRNA expression of E-cad in the nude mice with lateral lymph node metastasis was significantly lower than that in the mice without lateral lymph node metastasis (t=7.85, P< 0.05). Conclusions The serum level of E-cad may be closely associated with the lymphatic metastasis of rectal cancer, and the mRNA and protein expressions of E-cad in colorectal cancer tissue were weak or absent, leading to a decrease of adhesion ability between cancer cells, and promote the invasion and metastasis of cancer cells.