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Int J Cancer. 1998 May 29;76(5):671-6.

Human Trop-2 is a tumor-associated calcium signal transducer.

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1
Department of Cell Biology and Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro (Chieti), Italy.

Abstract

Trop-2/EGP-1/GA733-1 is a recently identified cell surface glycoprotein highly expressed by human carcinomas. The cytoplasmic tail of Trop-2 possesses potential serine and tyrosine phosphorylation sites and a phosphatidyl-inositol binding consensus sequence. Thus, we investigated whether Trop-2 might be a functional signaling molecule. Using the fluorescent probe Fura-2, we assayed the cytoplasmic calcium levels in human cancer cells stimulated with anti-Trop-2 or control antibodies. Three anti-Trop-2 MAbs, Rs7-7G11, MOv16 and 162-46.2 specifically induced a transient intracellular calcium level increment in up to 40% of the experiments performed. Polyclonal antisera recognizing recombinant Trop-2 molecules possessed a much lower stimulation efficiency. The average latency of antibody-induced Ca2+ rise for OvCa-432 cells was 64+/-26 sec. Internal Ca2+ concentrations reached peaks of 190+/-24 nM vs. basal levels of 61+/-4 nM and returned to baseline within 193+/-37 sec. Similar values were obtained in MCF-7 cells. For comparison, stimulation of P2-purinergic receptors on MCF-7 and OvCa-432 cells induced a Ca2+ rise in most cases, leading to average internal Ca2+ concentrations of 297+/-41 and 391+/-39 nM, respectively. Our findings show that Trop-2 transduces an intracellular calcium signal, are consistent with the hypothesis that it acts as a cell surface receptor and support a search for a physiological ligand.

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