Abstract
The peptide N-formyl-Met-Leu-Phe stimulates chemotaxis and metastasis in rat Walker carcinosarcoma cells by a receptor-mediated pathway. Since oxygen radical generation follows chemotactic stimulation in leukocytes, we looked for similar responses in the Walker tumor. Upon incubation with 10-6 m N-formyl-Met-Leu-Phe, Walker cells elicited chemiluminescence in the presence of 5 × 10-5 m luminol. The response peaked within 2 min and was maintained for >20 min; it was dose dependent with a 50% maximal effective dose (ED50) value of 4.5 × 10-8 m, comparable to the 50% maximal effective dose value for chemotaxis. The responses were significantly reduced but not abolished in the absence of calcium in the external medium and were elicited by the ionophore A23187. The lipoxygenase inhibitor nordihydroguaiaretic acid had almost no effect in decreasing the response, while flurbiprofen, a cyclooxygenase inhibitor was very effective at 10-6 m. Evidence for the generation of oxygen radicals included: (a) marked inhibition of light emission in the absence of oxygen; (b) inhibition in the presence of superoxide dismutase, catalase, and mannitol; and (c) dose-dependent reduction of acetylated cytochrome c. We postulate that activation of circulating tumor cells may facilitate metastasis by the release of toxic oxygen species.
Footnotes
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↵1 Supported by a grant from the National Cancer Institute of Canada. To whom requests for reprints should be addressed, at Department of Pathology, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada, L8N 3Z5.
- Received January 15, 1987.
- Revision received May 26, 1987.
- Accepted June 2, 1987.
- ©1987 American Association for Cancer Research.
Volume 47, Issue 18
