集落刺激因子-1及其受体对乳腺癌荷瘤鼠肿瘤生长的影响
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摘要
目的探讨CSF-1及其受体对乳腺癌荷瘤鼠肿瘤体积以及对其免疫器官包括骨髓、胸腺、淋巴结和脾的影响。方法将4T1细胞(1×107/只)重悬于PBS液接种于Balb/c小鼠左腋皮下,建立荷乳腺癌小鼠模型为实验组,同时培养相同条件的对照组。检测成瘤率,测量肿瘤体积的变化并绘制成图;成瘤后为实验组小鼠注射CSF-1及其受体,观察一段时间后同时处死两组小鼠,采用半定量RT-PCR技术检测鼠脾脏中CSF-1的表达;采用MTT比色法检测小鼠的肿瘤、脾脏、骨髓中细胞的增殖功能。结果4T1细胞接种后小鼠的成瘤率为100%,成瘤潜伏期平均为7~10天;实验组小鼠瘤体的增长速度快于对照组;RT-PCR的电泳结果显示,实验组小鼠的脾脏CSF-1的mRNA的表达量上升;MTT结果表明,CSF-1作用之后的实验组小鼠的肿瘤细胞和免疫细胞增殖活性升高,发挥了强大的免疫抑制功能,促进肿瘤的增长;增殖活跃的骨髓和脾细胞呈现免疫抑制表型。结论 CSF-1及其受体对乳腺癌荷瘤鼠肿瘤的生长有促进作用。
Objective To study the influence of colony stimulating factor-1(CSF-1) and its receptor on cancer cells and immune cells of breast cancer mice and to explore their effects on tumor size, volume and immune system including marrow, thymus, lymphonodus and spleen. Methods 4T1 cell(1×107/PBS) was inoculated in the left subcutaneous of Balb/c mice in order to establish the mice model with breast cancer. Then tumor formation rate, average weight and area change of tumor were measured. CSF-1 and its receptor were injected into experimental mice after tumor was formed, and these mice were killed after observation. The expression of CSF-1 in the spleen of mice was tested by semi-quantitative RT-PCR. The proliferation of T lymphocyte in the spleen and bone marrow were detected by MTT colorimetry. Results After the continuous improvement, tumor formation rate of 4T1 breast cancer was 100% and tumor latency was 7-10 days. After the injection of CSF-1, we found that tumor growth rate of the experimental mice was higher than that of control group. RT-PCR and electrophoresis results revealed that expression of CSF-1 was increased in the spleen of tumor-bearing mice.MTT results showed that the proliferation of immune lymphocytes and tumor cells was increased after CSF-1 treatment. Active proliferation of bone marrow and spleen cells exhibited immunosuppressive phenotype. Conclusion CSF-1 and its receptor could promote the growth of breast cancer tumor in mice.
Objective To study the influence of colony stimulating factor-1(CSF-1) and its receptor on cancer cells and immune cells of breast cancer mice and to explore their effects on tumor size, volume and immune system including marrow, thymus, lymphonodus and spleen. Methods 4T1 cell(1×107/PBS) was inoculated in the left subcutaneous of Balb/c mice in order to establish the mice model with breast cancer. Then tumor formation rate, average weight and area change of tumor were measured. CSF-1 and its receptor were injected into experimental mice after tumor was formed, and these mice were killed after observation. The expression of CSF-1 in the spleen of mice was tested by semi-quantitative RT-PCR. The proliferation of T lymphocyte in the spleen and bone marrow were detected by MTT colorimetry. Results After the continuous improvement, tumor formation rate of 4T1 breast cancer was 100% and tumor latency was 7-10 days. After the injection of CSF-1, we found that tumor growth rate of the experimental mice was higher than that of control group. RT-PCR and electrophoresis results revealed that expression of CSF-1 was increased in the spleen of tumor-bearing mice.MTT results showed that the proliferation of immune lymphocytes and tumor cells was increased after CSF-1 treatment. Active proliferation of bone marrow and spleen cells exhibited immunosuppressive phenotype. Conclusion CSF-1 and its receptor could promote the growth of breast cancer tumor in mice.
引文
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[7]Cui J,Yang DH.CSF-1 receptor/c-fms and liver cancer[J].Shi Jie Hua Ren Xiao Hua Za Zhi,2000,8(6):696-7.[崔俊,杨冬华.CSF-1受体/c-fms与肝癌[J].世界华人消化杂志,2000,8(6):696-7.]
[2]Chambers SK,Kacinski BM,Ivins CM,et al.Overexpression of epithelial macrophage colony-stimulating factor(CSF-1)and CSF-1 receptor:a poor prognostic factor in epithelial ovarian cancer,contrasted with a protective effect of stromal CSF-1[J].Clin Cancer Res,1997,3(6):999-1007.
[3]Yang DH,Liu WW,Gu JR.Expressions of IGF-I,IGF-II receptor and CSF-1 receptor of/c-fms oncogene in hepatocellular carcinomas and adjacent non-tumor tissues[J].Di San Jun Yi Da Xue Xue Bao,1992,14(1):100.[杨冬华,刘为纹,顾健人.IGF-II、IGF-II受体和CSF-1受体/c-fms癌基因产物在肝癌及癌旁肝组织的表达[J].第三军医大学学报,1992,14(1):100.]
[4]Pollard JW.Role of colony-stimulating factor-1 in reproduction and development[J].Mol Reprod Dev,1997,46(1):54-60.
[5]Kacinski BM.CSF-1 and its receptor in breast carcinomas and neoplasms of the female reproductive tract[J].Mol Reprod Dev,1997,46(1):71-4.
[6]Qian LF,Wu KF,Geng YQ,et al.Biological effect of monoclonal antibodies against CSF1&CSF 1R on human hepatic cancer cells transplanted in nude mice[J].Zhong Liu,1997,17(4):207-8.[钱连芳,吴克复,耿以琪,等.集落刺激因子1及其受体的单抗对人肝癌细胞在裸鼠体内生长的抑制作用[J].肿瘤,1997,17(4):207-8.]
[7]Cui J,Yang DH.CSF-1 receptor/c-fms and liver cancer[J].Shi Jie Hua Ren Xiao Hua Za Zhi,2000,8(6):696-7.[崔俊,杨冬华.CSF-1受体/c-fms与肝癌[J].世界华人消化杂志,2000,8(6):696-7.]