Different metastatic potentials of ras- and src-transformed BALB/c 3T3 A31 variant cells
✍ Scribed by Masaaki Tatsuka; Takahide Ota; Nobuyuki Yamagishi; Yasunari Kashihara; Morimasa Wada; Naoki Matsuda; Hiromi Mitsui; Motoharu Seiki; Shizuo Odashima
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 887 KB
- Volume
- 15
- Category
- Article
- ISSN
- 0899-1987
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✦ Synopsis
The metastatic phenotype of tumor cells is thought t o be induced by an aberrant signaling cascade or cascades that are different from those required for tumorigenicity. Oncogene-transfected cells with different tumorigenicities and metastatic potentials have been used t o identify such pathways and responsible mol- ecules. However, oncogenes that can induce tumorigenicity in recipient cells also frequently induce the metastatic phenotype at the same time. The difficulty in obtaining cell lines that are tumorigenic but not metastatic has hampered such studies. In this report, we transfected the activated c-Ha-ras oncogene into BALB/c 3T3 A31 variant cells and found that the transfectants were tumorigenic but they did not form metastatic lung nodules in the experimental metastasis assay. The phenotype was very stable and was maintained during cultivation. On the other hand, the metastatic potentials of either the transfected cells or the original variant cells could be induced by transfection of the v-src oncogene. The src transfectants formed extensive nodules in lung when injected into the tail veins of congeneric mice. The cell motility of the metastaticsrc transfectants on Matrigelcoated dishes was greater than that of theras transfectants. Thesrc transfectants were also invasive in Matrigel when analyzed on a filter. These variant cells transformed by the ras and src oncogenes will be a useful system for identifying the signaling cascades responsible for the metastatic potential of tumors.