Establishment of a spontaneous metastasis tumor model for human ErbB-2 vaccine

Abstract

Human ErbB-2 (Her-2) is a critical target for cancer immunotherapy, and its over-expression can promote cancer migration and invasion. Compared with passive antibody therapy, vaccination treatment is more effective in the prevention of cancer recurrence. BALB-neuT mouse is a spontaneous metastasis tumor model used for testing the anti-tumor metastatic effect of rat ErbB-2 (neu) vaccine. However, no spontaneous metastasis tumor model used for evaluating Her-2 vaccine has been developed. In the current study, we attempted to use murine melanoma cell lines to establish a stable spontaneous metastasis tumor model for Her-2 vaccines. We developed Her-2-positive B16F10 and B16BL6 cell lines expressing similar Her-2 levels as the typical human tumor cell line SKBR-3. Results showed that Her-2-positive B16BL6, rather than B16F10, cell line could effectively and spontaneously transfer to the lungs approximately 28days after the removal of primary tumors because it has stronger adhesion and invasion capacities. A stable spontaneous metastasis model was developed through in vivo screening of Her-2-positvie B16BL6 cells twice. This model was successfully applied in the analysis of the anti-metastatic efficacy of a tumor vaccine based on heat shock protein. Thus, we first established a spontaneous metastasis model that stably expresses Her-2 at similar levels as human cancers. This model can be used to evaluate the anti-metastatic efficacy of Her-2 vaccine.