L-选择素 整合素αL及整合素β2的表达与TA2小鼠乳腺癌多器官转移的关系研究

Relationship between Expression of L-selectin,Integrin αL and Integrin β2 and Multiple-organ Metastasis of Breast Cancer in TA2 Mice

目的:探讨L-选择素、整合素αL及整合素β2的表达与TA2小鼠乳腺癌多器官转移的关系。方法:收集天津医科大学附属肿瘤医院病理科保存的高转移性(可发生多器官转移,A组)、低转移性(无远处转移,B组)TA2小鼠乳腺癌及A组肺、肝和脾转移瘤标本,观察肿瘤特征,利用免疫组化方法检测原发瘤及转移瘤组织中整合素αL、整合素β2、L-选择素的表达情况,并利用Real-time PCR方法检测A组和B组原发瘤组织中上述分子mRNA的相对表达水平。结果:A组全组原发肿瘤均见明显出血和坏死,均为低分化或未分化癌,可观察到血管生成拟态,均出现了明显的肺、肝和脾转移。A组和B组原发肿瘤组织中整合素αL和L-选择素的平均阳性细胞百分比分别为24.81% vs 10.47%和39.81%vs 16.75%,二者在A组中的表达均显著高于B组(Z=-2.31,Z=-2.14;P<0.05),而整合素β2的表达在A组与B组间无显著性差异;A组原发瘤及其肺、肝和脾转移瘤中L-选择素平均阳性细胞百分比分别为39.81%、39.07%、62.09%和55.51%,其中肝转移瘤中平均阳性细胞百分比显著高于原发瘤(Z=-2.24,P=0.025),而整合素αL、β2平均阳性细胞百分比在转移瘤与原发瘤间均无显著性差异。整合素αL和L-选择素mRNA的相对表达水平在A组原发瘤显著高于B组(Z=-3.47,Z=-3.32;P<0.01)。结论:TA2小鼠乳腺癌细胞可表达L-选择素、整合素αL和β2,其中L-选择素的表达可能与其肝转移有关。

Objective： To investigate the effect of the L-selectin, integrin aL and integrin β2 expressions on the multiple-organ metastasis of breast cancer of TA2 mice. Methods： The pathologic character of spontaneous breast cancer with multiple-organ metastasis （high metastasis, Group A） and without distant metastasis （low metastasis, Group B） were observed by macroscopy and H＆E staining sections. The level of the L-selectin, integrin eL and integrin β2 expressions in Group A, Group B and the metastatic tumors of Group A were detected using the immunohistochemical method. The level of the mRNA of L-selectin, integrin aL and integrin β2 relative expressions in the prmary tumors of Group A and Group B were detected by Real-time PCR method. Results： Hemorrhage and necrosis were visibly seen in all the primary tumors of the Group A which were poorly differentiated or undifferentiated. Pulmonary, hepatic and splenic metastases, and angiogenetic mimicry were observed in these tumors. The average positive cell percentage of integrin aL and L-selectin in pdmary tumors of Group A and Group B were 24.81% vs.10.47% and 39.81% vs. 16.75%, respectively. The expressions of the proteins were significantly higher in Group A than in Group B （Z=-2.31, -2.14, respectively; P〈0.05）, while there was no significant difference in the expression of integdn β2 between the two groups. In Group A, the average levels of L-selectin expression were 39.81%, 39.07%, 62.09% and 55.51% in the primary tumors, and the pulmonary, hepatic and splenic metastatic tumors, respectively, among which the average expression of L-selectin was significantly higher in liver metastatic tumor than in primary tumor （Z=-2.24, P=-0.025）, while there was no markedly difference in the expression of integrin aL and integrin β2 between the primary and metastastic tumor. The levels of L-selectin and integrin aL mRNA relative expression were significantly higher in the primary tumros of Group A than in those of Group B （Z=-3.32, -3.47; P〈 0.01）. Conclusion： L-selectin, integrin aL and integrin β2 could be expressed by spontaneous breast cancer cells of TA2 mice and the expression of L-selectin might be related to liver metastasis.