Metastatic variants of the B16 melanoma: metastasis is related to environmental conditions. Phenotypic changes in vitro and metastatic colonization potential in nude mice.

Variants of B16 melanoma exhibit strikingly different metastatic potential in AY/a (YB16 tumours) and a/a C57BL/6J (MB16 tumours) syngeneic mice. This study focused on relative pigmentation and metastatic potential in eight subline cultures initiated from B16 control and YB16 and MB16 tumours. During 6 months of in vitro growth in minimal essential medium, cells displayed a continuous decrease in their ability to form spontaneous lung colonies in 140 syngeneic mice with only persistence of enhanced metastasis-related characteristics depending on genetic change in yellow AY/a mice. Conversely, in a parallel experiment in 101 syngeneic mice in vitro, cells had a greater capacity to generate experimental metastases; this might be related to successive different environmental factors. In order to compare these prior results obtained in syngeneic mice, the above eight secondary cell lines were inoculated subcutaneously into Swiss nude mice. The primary tumours thus obtained were then serially transplanted monthly during 4 months. The new results obtained in a total of 277 mice showed that metastatic properties of cells were enhanced or restored in nude mice. Various tumour cell environments seem to be responsible for selective pressures that determine the melanoma metastatic potential. New, enhanced, heritable, metastasis-related characteristics can occur in melanoma cells as a result of genetic and metabolic changes and immunologic deficiency of the host. Apparent tumour-host relationship should not be neglected, since it has a clear influence on neoplastic diversity and malignant behaviour.