ORTHOTOPIC HUMAN-MELANOMA XENOGRAFT MODEL SYSTEMS FOR STUDIES OF TUMOR ANGIOGENESIS, PATHOPHYSIOLOGY, TREATMENT SENSITIVITY AND METASTATIC PATTERN

Adequate tumour models are a prerequisite in experimental cancer resea rch. The purpose of the present work was to establish and assess the v alidity of four new orthotopic human melanoma xenograft model systems (A-07, D-12, R-18, U-25). Permanent cell lines were established in mon olayer culture from subcutaneous metastases of four different melanoma patients by using an in vivo-in vitro procedure, and cells from these lines were inoculated intradermally in Balb/c nu/nu mice to form rumo urs. Individual xenografted tumours of the same line differed substant ially in growth and pathophysiological parameters, probably as a conse quence of differences between inoculation sites in host factors which influence tumour angiogenesis. Nevertheless, xenografted tumours of di fferent lines showed distinctly different biological characteristics. Several biological characteristics of the donor patients' tumours were retained in the xenografted tumours, including angiogenic potential; growth, histopathological and pathophysiological parameters; and sensi tivity to radiation, heat and dacarbazine treatment. Moreover, the org an-specific metastatic pattern of the xenografted tumours reflected th e pattern of distant metastases in the donor patients. The organs of p reference for distant metastases were lungs (A-07, D-12), lymph nodes (R-18) and brain (U-25). R-18 lymph node metastases and U-25 brain met astases developed in the absence of lung involvement. The four orthoto pic human melanoma xenograft model systems show great promise for futu re studies of tumour angiogenesis, pathophysiology, treatment sensitiv ity and metastatic pattern.