SCID MICE MODEL FOR THE IN-VIVO STUDY OF HUMAN ONCOTHERAPY - STUDIES ON THE GROWTH AND METASTASIS OF HUMAN LUNG-CANCER

For the study of the growth and metastasis of human lung cancer, we established a severe combined immunodeficient (SCID) mouse model for engraftment of intact human lung-cancer tissue dissected from patient specimens. Small fragments of human lung-cancer tissues (14 cases) obtained from surgery or autopsy were implanted into the mammary fat pads of SCID mice. Seven of the fourteen cases (50%) showed an evident enlargement of the implanted lung-cancer tissue, the histopathology of which was almost identical to that of the original cancer tissues for as long as 2 months following implantation. There was slight correlation between the implantation success rate and the clinical stage of the patient at implantation. A second implantation of cancer tissues on four of these cases was successful. In contrast, no significant enlargement of the implanted tissue was observed in the cases of normal human peripheral-lung tissues (five cases), but a bronchial epidermal feature was observed in all of them. Matrigel (Collaborative Research, Bedford, MA) coating of the tissues significantly increased the growth rate of lung-cancer implants, and a high correlation (R=O.806) between the size of the implanted human lung-cancer tissues and carcinoembryonic antigen levels in the SCID mice was seen. Additionally, human lung-cancer cell lines subcutaneously injected into the backs of mice showed more metastatic lesions in the lungs and lymph nodes of SCID mice than in nude mice. Also, fresh human lung cancer metastasized to the lymph nodes and lungs of SCID mice. The results demonstrate the utility of SCID mice as recipients of human lung-cancer tissue and the applicability of this model to the in vivo study of mechanisms of human lung-cancer growth and metastasis.