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Establishing a link between oncogenes and tumor angiogenesis
R S Kerbel1, A Viloria-Petit, F Okada
1Division of Cancer Biology Research, Sunnybrook Health Science Centre, Toronto, Ontario, Canada. kerbel@srcl.sunnybrook.utoronto
Molecular Medicine (Cambridge, Mass.)
|June 27, 1998
Summary
Oncogenes promote tumor growth not only by direct cell proliferation but also by regulating angiogenesis, a mechanism previously unappreciated in standard cell cultures. This finding impacts the development of targeted cancer therapies.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Oncogenes and proto-oncogenes are critical regulators of cell growth and survival.
- Traditional in vitro studies using pure tumor cell cultures have limitations in revealing complex tumor microenvironment interactions.
- The role of oncogenes in tumor angiogenesis has been historically underestimated.
Purpose of the Study:
- To highlight the indirect role of oncogenes in stimulating tumor growth via angiogenesis.
- To explain why this pro-angiogenic function was not readily observed in previous experimental models.
- To underscore the significance of oncogene-driven angiogenesis in cancer development.
Main Methods:
- Utilized reconstituted organ cultures (mouse prostate gland) to study oncogene function in a more complex environment.
- Investigated the effects of oncogenes like ras and myc on tumor angiogenesis.
- Reviewed existing literature and early clinical trial data on signal transduction inhibitors.
Main Results:
- Mutant oncogenes and overexpressed proto-oncogenes can indirectly promote tumor cell growth by regulating angiogenesis.
- Early studies using reconstituted organ cultures provided initial evidence for oncogene involvement in tumor angiogenesis.
- This indirect mechanism is not detectable in standard tissue culture models.
Conclusions:
- Oncogenes play a significant role in tumor development through the regulation of angiogenesis.
- Understanding this indirect mechanism is crucial for developing effective anti-cancer therapies.
- Findings may influence the clinical application of signal transduction inhibitors targeting pathways like EGF receptor.