BAP31胞内抗体的构建及其影响肿瘤干细胞增殖与分化的机制研究

Tumor stem cells (TSCs) are the real reasons for tumor initiation, recurrence, malignant metastasis and tolerance to chemotherapy. Therefore, it is a key issue to cure cancer by targetting the genes related to the cancer initiation. BAP31 is identified as a new tumor associated antigen and can inhibit the apoptosis of tumor cells. Our previous study found that block partial function of BAP31 could inhibit the proliferation of bladder cancer cells (UC6). Combination with the recent reports that BAP31 can promote stem cells self-renewal, pluripotency and inhibit apoptosis, we speculate that BAP31 may be closely related to the proliferation and differentiation of TSCs. Therefore, we intend to take bladder tumor stem cells (UC6-TSCs) as the object of the research and construct endoplasmic reticulum-retained anti-BAP31 (VH) intrabody. We want to achieve the purpose of inhibiting the proliferation of TSCs, inducing TSCs apoptosis and thereby effective killing of TSCs by blocking the function of BAP31 through the interaction of BAP31 with anti-BAP31 antibody. We aimed to clarify the potential mechanism of using anti-BAP31-VH-antibody to kill TSCs and provide adequate theoretical basis for cancer treatment by blocking the function of BAP31 through intrabody in TSCs.

肿瘤干细胞（TSCs）是肿瘤形成、复发、恶性转移和耐受放化疗的根源。因此，寻找TSCs中与肿瘤发生密切相关的基因，开展靶向性杀伤，成为根治恶性肿瘤的关键问题。BAP31被发现是一种新的肿瘤相关抗原，可以抑制肿瘤细胞凋亡。我们前期研究发现：封闭BAP31在膀胱癌（UC6）细胞中的部分功能后，UC6细胞的增殖受到抑制。结合近期的报道：BAP31可以促进干细胞自我更新、维持其多潜能分化性、抑制凋亡。我们推测：BAP31与TSCs的增殖与分化密切相关。为此，我们拟以膀胱癌干细胞（UC6-TSCs）为研究对象，构建内质网滞留型BAP31胞内抗体。通过抗体与BAP31的相互作用“定向封闭”BAP31的功能，抑制TSCs增殖、诱导分化，从而达到有效杀灭TSCs的目的。阐明BAP31胞内抗体杀灭TSCs机理，为确立将“定向封闭”BAP31蛋白在TSCs中的功能作为治疗癌症的新策略提供充分的理论依据。

肿瘤干细胞（TSCs）是肿瘤形成、复发、恶性转移和耐受放化疗的根源。因此，寻找TSCs中与肿瘤发生密切相关的基因，开展靶向性杀伤，成为根治恶性肿瘤的关键问题。BAP31被发现是一种新的肿瘤相关抗原，可以抑制肿瘤细胞凋亡。我们前期研究发现：封闭BAP31在膀胱癌（UC6）细胞中的部分功能后，UC6细胞的增殖受到抑制。结合近期的报道：BAP31可以促进干细胞自我更新、维持其多潜能分化性、抑制凋亡。我们推测：BAP31与TSCs的增殖与分化密切相关。为此，我们拟以膀胱癌干细胞（UC6-TSCs）为研究对象，构建内质网滞留型BAP31胞内抗体。通过抗体与BAP31的相互作用“定向封闭”BAP31的功能，抑制TSCs增殖、诱导分化，从而达到有效杀灭TSCs的目的。阐明BAP31胞内抗体杀灭TSCs机理，为确立将“定向封闭”BAP31蛋白在TSCs中的功能作为治疗癌症的新策略提供充分的理论依据。