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

Int J Cancer. 1998 May 29;76(5):671-6. doi: 10.1002/(sici)1097-0215(19980529)76:5<671::aid-ijc10>;2-7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Adenosine Triphosphate / physiology
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibody Specificity
  • Antigens, Neoplasm / pharmacology
  • Antigens, Neoplasm / physiology*
  • Antigens, Surface / pharmacology
  • Antigens, Surface / physiology*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Calcium / metabolism*
  • Cell Adhesion / physiology
  • Cell Adhesion Molecules*
  • Cytosol / physiology
  • Epithelial Cell Adhesion Molecule
  • Female
  • Flow Cytometry
  • Humans
  • Immunoconjugates / pharmacology
  • Membrane Glycoproteins / pharmacology
  • Membrane Glycoproteins / physiology*
  • Mice
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Recombinant Proteins / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Tumor Cells, Cultured


  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Antigens, Surface
  • Cell Adhesion Molecules
  • Epithelial Cell Adhesion Molecule
  • Immunoconjugates
  • Membrane Glycoproteins
  • Recombinant Proteins
  • Adenosine Triphosphate
  • Calcium