Development of androgen-independent spindle cell tumors from androgen-dependent medullary Shionogi carcinoma 115 in androgen-depleted nude mice.

When Shionogi carcinoma 115 (SC115, undifferentiated medullary carcinoma showing compact cell pattern and containing androgen receptor) was transplanted into male and female DS mice, it grew only in males. In contrast to this strict androgen dependency in DS hosts, tumors composed of spindle-shaped cells appeared in more than 80% of cases when SC115 tumor was inoculated into female or castrated male nude athymic (BALB/c-nu/nu) recipients. These spindle cell tumors neither contained cytosol androgen receptor nor showed biologically defined androgen dependency. As spindle cell tumors could be serially transplanted in DS mice but not in BALB/c-+/+ mice and as the original SC115 (medullary carcinoma showing a compact cell pattern) tumor and the spindle cell tumor had many identical chromosome abnormalities, these two types of tumors seem to have a common origin in spite of their morphological, biochemical, and biological differences. Since spindle cells could not be detected histologically in SC115 tumors maintained in intact male DS mice, the present results seem to suggest that SC115 cells may change their morphological, biochemical, and biological characteristics within one passage in androgen-depleted nude athymic mice.