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Different metastatic potentials of ras- and src-transformed BALB/c 3T3 A31 variant cells
M Tatsuka1, T Ota, N Yamagishi
1Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Japan.
Abstract:
The metastatic phenotype of tumor cells is thought to 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 to identify such pathways and responsible molecules. 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 modules 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 metastatic src transfectants on Matrigel-coated dishes was greater than that of the ras transfectants. The src 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.
Insights
Tumorigenic cells lacking metastatic potential were created using the c-Ha-ras oncogene. The v-src oncogene induced metastatic capabilities, offering a new model for studying cancer metastasis signaling pathways.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Tumor cell metastasis is driven by signaling pathways distinct from those causing tumorigenicity.
- Identifying these specific pathways is challenging because oncogenes often induce both phenotypes simultaneously.
Purpose of the Study:
- To develop a cell model for studying metastatic potential.
- To differentiate between oncogenes inducing tumorigenicity versus metastasis.
Main Methods:
- Transfection of BALB/c 3T3 A31 variant cells with activated c-Ha-ras oncogene.
- Transfection with v-src oncogene to assess metastatic potential induction.
- Experimental metastasis assay in mice.
- Cell motility and invasion assays using Matrigel.
Main Results:
- c-Ha-ras transfectants were tumorigenic but non-metastatic, exhibiting stable phenotypes.
- v-src transfection induced metastatic potential in both original and ras-transfected cells.
- Src transfectants showed increased cell motility and Matrigel invasion compared to ras transfectants.
Conclusions:
- The ras and src oncogene-transformed cells provide a valuable system for dissecting signaling cascades involved in tumor metastasis.
- This model facilitates the identification of molecular mechanisms underlying metastatic potential.