CALCIUM-MEDIATED SIGNAL-TRANSDUCTION - BIOLOGY, BIOCHEMISTRY, AND THERAPY

The process of proliferation, invasion and metastasis is a complex one which involves both the autonomy of the malignant cells and their int eraction with the cellular and extracellular environments. The way in which the tumor cells respond to cellular and extracellular stimuli is regulated through transduction of those signals and translation into cellular activity. Transmembrane signal transduction involves three ma jor categories of events: ion channel activation, transmission through guanine nucleotide binding protein intermediates with production of s econd messengers, and phosphorylation events. A frequent common denomi nator of these different pathways is a cellular calcium homeostasis. C alcium may be both a result of and a regulator of many of these signal transduction pathways and has been shown to have a role in the regula tion of proliferation, invasion, and metastatic potential. The underst anding and application of the basic tenets of these pathways to tumor cell proliferation, invasion, and metastases opens a new target for th erapeutic intervention. We have identified a novel agent, CAI, which t hrough inhibition of stimulated calcium influx inhibits proliferation and migration in vitro, and growth and dissemination in human cancer x enografts in vivo. CAI offers a new a approach to cancer therapy, sign al transduction therapy.