Loss of Mesothelin Expression by Mesothelioma Cells Grown In Vitro Determines Sensitivity to Anti-Mesothelin Immunotoxin SS1P

Anticancer Research. 2012 Dec;32(12):5151-8. [Link]

Zhang J, Qiu S, Zhang Y, Merino M, Fetsch P, Avital I, Filie A, Pastan I, Hassan R.

Laboratory of Molecular Biology, National Cancer Institute, 37 Convent Drive, Room 5116, Bethesda, MD 20892-4264, U.S.A. hassanr@mail.nih.gov.

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.