CD55 可能成为结直肠癌治疗的新靶点

In the early stage, our research group injected lentivirus carrying blood type A antigen into tumors as a drug, and the tumor volume of mice was significantly reduced.

We speculate that the complement system plays an important role in anti-tumor therapy, but the specific components are unknown. A mouse model containing blood type antibodies was established. After the mouse axilla formed tumors, lentivirus carrying different blood type antigens was used for treatment. On this basis, NK cell activity was inhibited and the complement system of the body was eliminated. Tumor formation was observed. Flow cytometry was used to observe the changes in tumor tissue and peripheral blood immune cells. Immunohistochemistry was used to observe NK cells in tumors. Proteomics was used to screen differential complement components. Transcriptomics was used to observe the gene expression differences of CT26 cells overexpressing CD55, and RT-PCR was used for verification. The changes of CEA, CA199, CA125, CA153, D-D dimer, total white blood cell count, neutrophil ratio, lymphocyte ratio, monocyte ratio, and fibrinogen in the simple colorectal cancer group, simple liver metastasis group, simple lung metastasis group, and multiple organ metastasis group were retrospectively analyzed, and ROC curves were used for evaluation; ELISA method was used to detect the changes in CD55 content in the healthy group, simple colorectal cancer group, simple liver metastasis group, simple lung metastasis group, and multiple organ metastasis group, and ROC curves were used to evaluate its clinical diagnostic ability.

CCK8 and EdU methods were used to detect cell proliferation. Scratch assay and transwell assay were used to observe cell migration. Western blotting was used to observe the changes of MMP9, Vimentin and -SMA. After the lentivirus carrying blood type A antigen was injected into the axillary tumor of mice, the tumor volume was significantly reduced compared with the control group. The proportion of NK cells in tumor tissue increased significantly. Using antibodies to block NK cell surface activation receptors and eliminate the complement system, both treatments reduced the therapeutic effect. Both blood type B and Rh blood type antigens can significantly reduce tumor volume.

Eliminating complement in the body increases the incidence of liver metastasis. The proliferation degree of overexpressed CD55 in tumors is significantly increased. CD55 overexpression can significantly increase the expression of CCL2, CCL3, CCL4, CCL7, CXCL12, TLR7, CSFR1, TCAM, TNF, BTK and MMP9.

CEA and CA199 are of certain value in judging liver metastasis, and CD55 has better diagnostic efficacy. Complement significantly inhibits cell proliferation. CD55 significantly promotes CT26 proliferation and migration ability. CD55 is a potential tumor promoter and diagnostic marker for colorectal cancer.