黏蛋白1多肽通过small-MUC1蛋白抑制肿瘤细胞生长

目的：探讨黏蛋白1（mucin 1，MUC1）串联重复序列多肽(简称黏蛋白1多肽，MUC1多肽)对肿瘤细胞生长抑制的作用机制。方法：MUC1多肽与多种肿瘤细胞Jurkat、Raji、U937、MCF7、SMMC7721及活化的T细胞、小鼠巨噬细胞RAW264.7共同培养，观察MUC1多肽对上述细胞生长的影响；建立BABL/c小鼠Jurkat细胞皮下移植瘤动物模型，应用MUC1多肽进行治疗；采用GST免疫沉降实验鉴定与MUC1多肽结合的肿瘤细胞表面蛋白。结果：MUC1多肽对Jurkat、Raji、U937、MCF7和SMMC7721细胞的生长均有抑制作用，对活化的T细胞和小鼠RAW264.7细胞生长无明显抑制作用。MUC1多肽对BABL/c小鼠皮下Jurkat细胞移植瘤的生长均有明显抑制作用（P<0.05）。GST免疫沉降实验显示，Jurkat 和MCF7细胞裂解上清中与MUC1多肽结合的蛋白可与两种抗MUC1串联重复序列抗体（GP1.4和HMPV）及抗胞内段抗体（Ab5）发生反应，相对分子质量大约115 000，提示可能是MUC1新的同种型，命名为small MUC1（sMUC1）。结论：MUC1多肽可通过与肿瘤细胞表面small MUC1蛋白的相互作用向细胞传导生长抑制信号

MUC1 peptide inhibits tumor cell proliferation by binding small-MUC1 protein

Objective:To investigate the inhibitory mechanism of mucin 1 tandem repeats peptide (MUC1 peptide) against the proliferation of tumor cells. Methods: Jurkat, Raji, U937, MCF-7, SMMC7721, activated T and RAW264.7 cells were co-cultured with MUC1 peptide; the inhibitory effects of MUC1 peptide on these cells were observed. Jurkat cell-inoculated BABL/c mouse model was established by s.c. injection of Jurkat cells, and then the tumor-bearing mice were treated with MUC1 peptide. The protein interacting with MUC1 peptide was identified by GST pull-down assay. Results: MUC1 peptide inhibited the proliferation of Jurkat, Raji, U937, MCF-7 and SMMC7721 cells, but had no measurable inhibitory effect on activated T cells and RAW264.7 cells. MUC1 peptide significantly inhibited the growth of implanted Jurkat tumors in BABL/c mice (P<0.05). The protein interacting with MUC1 peptide in the lysates of Jurkat and MCF-7 cells was confirmed by GST pull-down assay, with its molecular weight being approximately 115 000. The protein could bind specifically to anti-MUC1 tandem repeat antibodies (GP1.4 and HMPV) and anti-MUC1 cytoplasmic domain antibody (Ab5), indicating it might be a novel isotype of MUC1, and it was named small MUC1 (sMUC1). Conclusion: MUC1 peptide can transduce growth inhibitory signal by interacting with small MUC1 on the surface of tumor cells.