Growth and dissemination of human malignant melanoma cells in mice with severe combined immune deficiency

Abstract

Background: The severe combined immune deficiency (SCID) mouse is lacking mature B and T lymphocytes and may be permissive for human tumor growth and metastasis.

Experimental design: SCID mice received human melanoma cells of diverse origins including: 2 established cell lines, 4 early passage cell lines, and fresh or cryopreserved cells obtained directly from 9 patient biopsies. They were introduced into SCID mice via intraperitoneal, subcutaneous and intravenous injections.

Results: Tumor growth occurred with each of the 15 melanoma specimens for a take rate of 100% considering cell source. In addition, 60% of the 102 total mice injected displayed tumor growth in at least one site. The most consistent tumor growth (77%) occurred after intraperitoneal injection. Tumors developed in 41 and 48% of mice injected subcutaneously and intravenously, respectively. The mice developed both local tumor growth with palpable tumor nodules at injection sites and hematogenous and/or lymphatic dissemination to multiple sites in the abdominal and thoracic cavities. The number of metastases per animal averaged 16.3 and the number per organ ranged from 1 to 38. Melanotic and amelanotic tumor nodules obtained from a single patient retained their original characteristics with regard to melanin production after passage in the SCID mouse. The appearance of the human melanoma cells in SCID mouse tissues ranged from implants on the organ capsule to frank parenchymal organ involvement and vascular invasion. Some small foci of tumor were only detected using immunohistochemistry with monoclonal antibodies against the S-100 and HMB-45 to melanoma-related antigens.

Conclusions: We conclude that the SCID mouse consistently supports growth, invasion, and metastatic spread of human melanoma cells, including specimens obtained from fresh patient biopsies. The SCID mouse will serve as a relevant in vivo model for studying the biology of human malignant melanoma and screening new therapeutic agents.