We developed and evaluated an in vivo athymic nude mouse model for
tumor growth, angiogenesis,
metastasis, and
antineoplastic drug development.
Melanoma cell lines expressing
beta-galactosidase encoded by the Escherichia coli lac Z gene have been created by infecting an immortal murine melanocyte cell line with a recombinant retrovirus expressing the v-Ha-ras oncogene and lac Z to generate the MRB (
melanoma, ras,
beta-galactosidase) cell lines. The amelanotic,
phorbol ester-independent, transformed
melanoma cell lines developed
tumors rapidly when injected subcutaneously into nude mice, as well as experimental lung
metastases when injected i.v. into the tail vein.
beta-galactosidase-expressing subcutaneous
tumors and lung
metastases stained blue with
X-gal. The
melanomas produced in nude mice have been characterized by using various histochemical and immunohistochemical staining methods to detect
melanoma- and endothelial-cell-specific markers to determine the extent of neovascularization in MRB nude mouse
tumors. Optimal staining of endothelial cells involved in
tumor angiogenesis was observed by using
ADPase activity and antiangiotensin-converting
enzyme antibody staining. Attempts at indirect quantification of metastatic
tumor cell number within the lung by either
beta-galactosidase enzymatic activity or ELISA immunoreactivity were unsuccessful. However, the MRB cell lines should be useful in screening for and studying the mechanisms of action of
antineoplastic, antimetastatic, and angiostatic drugs in vivo in athymic nude mice.