Mitogenic signaling by substance P and bombesin-like neuropeptide receptors in astrocytic/glial brain tumor-derived cell lines.

Neuropeptides such as substance P (SP) and bombesin regulate many biological processes through binding to and activating their respective cell surface receptors. Recently, we reported that many astrocytic/glial-derived brain tumor cell lines express functional SP and bombesin receptors (43% and 85%, respectively). Activation of these neuropeptide receptors stimulates several signaling pathways that regulate transcription and translation leading to the induction of mitogenesis in several cell types including astrocytic brain tumor-derived cell lines. We have also shown that a number of signaling pathways are induced by SP and/or bombesin receptors in astrocytic/glial-derived brain tumor cell lines and demonstrated that inhibiting these path-ways by selective compounds such as PD 098059, tamoxifen, CGP 41251, and rapamycin blocks cell growth. In summary, mitogenic signaling by neuropeptides may play a role in brain tumor growth and/or tumor progression, and selective compounds capable of blocking mitogenic signaling have potential to be useful in the treatment of brain tumors.