Abstract |
It is not presently understood why a substantial proportion of established
human solid carcinoma cell lines lack the ability to form tumors in nude
mice (JNCI 59:221, 1977). The VAMT-1 cell line, which was established in
culture from a patient with the sarcomatoid variant of malignant pleural
mesothelioma, was chosen for study of this phenomenon. The original
surgical specimen was also directly grown in nude mice, and the resulting
tumor was sub-passaged for approximately three years. Although the
mesothelial and neoplastic nature of the cultured cells was supported by a
variety of characterization studies (including histochemistry, karyology,
and electron microscopy) this line repeatedly failed to produce tumors in
nude mice. However, when coinjections were performed with a histologically
distinctive human colon carcinoma cell line (RW-2982), tumorigenicity was
restored. The resultant "mixed tumor" grew with areas of both sarcomatoid
mesothelioma and mucogenic colonic carcinoma. Even with additional sub-
passage in the nude mouse, this tumor retained its mixed histology. Since
the VAMT-1 and RW-2982 lines grow exclusively as attached monolayer cells
and as floating mucous-coated organoid structures, respectively, the two
cell lines are easily separated in vitro. After four months (two sub-
passages) in nude mice the mixed tumor was re-established in culture and
the two component cell lines (which appeared unchanged) were separated.
Preliminary studies show that other genuinely tumorigenic cell lines will
also function as "feeder tumors" for the non-tumorigenic VAMT-1. In
summary, there exists a mechanism by which the coinjection of RW-2982
cells can restore tumorigenicity to the VAMT-1 cell line.
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