Loss of mesothelin expression by mesothelioma cells grown in vitro determines sensitivity to anti-mesothelin immunotoxin SS1P

Anticancer Res. 2012 Dec;32(12):5151-8.

Abstract

Background/aim: To determine if early passage tumor cells obtained from patients with mesothelioma continue to express the tumor differentiation antigen mesothelin and their sensitivity to the anti-mesothelin immunotoxin SS1P.

Materials and methods: Cell cultures were established from ascites or pleural effusion of 6 peritoneal and 3 pleural mesothelioma patients, respectively. These cells were evaluated for mesothelin expression by immunohistochemistry and flow cytometry.

Results: Although mesothelin was highly expressed in tumor biopsies of all patients, only 3 out of 9 malignant effusions from these patients when grown in short-term culture showed strong mesothelin positivity by IHC. By flow cytometry, the number of mesothelin sites per cell was variable ranging from 580 to 210,000 sites/cell. Cells with strong mesothelin expression by IHC and increased number of mesothelin sites/cell were sensitive to SS1P.

Conclusions: Most mesothelioma tumors loose mesothelin when grown in vitro and the sensitivity of these cells to SS1P is dependent on the number of mesothelin sites/cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology*
  • Ascites / pathology
  • Female
  • Flow Cytometry
  • GPI-Linked Proteins / biosynthesis
  • GPI-Linked Proteins / deficiency*
  • GPI-Linked Proteins / immunology
  • Humans
  • Immunohistochemistry
  • Male
  • Mesothelin
  • Mesothelioma / drug therapy*
  • Mesothelioma / metabolism*
  • Mesothelioma / pathology
  • Middle Aged
  • Peritoneal Neoplasms / drug therapy
  • Peritoneal Neoplasms / metabolism
  • Peritoneal Neoplasms / pathology
  • Pleural Effusion, Malignant / pathology
  • Pleural Neoplasms / drug therapy
  • Pleural Neoplasms / metabolism
  • Pleural Neoplasms / pathology
  • Tumor Cells, Cultured
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • GPI-Linked Proteins
  • SS1(dsFv)PE38
  • Mesothelin