Mesothelin expression in human lung cancer.
OBJECTIVE
To investigate mesothelin as a new target for immunotherapy in lung cancer.


METHODS
Mesothelin mRNA and protein expression were assessed by reverse transcription-PCR, immunoblotting, and immunohistochemistry in human lung cancer specimens. Expression was also characterized in human lung cancer cell lines by flow cytometry and immunoblotting. The SS1P immunotoxin specific for mesothelin was assessed for its cytotoxic activity against lung cancer cells.


RESULTS
We found that mesothelin mRNA was expressed in 83% of lung adenocarcinomas (10 of 12 patients). The mesothelin precursor protein was detected in 82% of lung adenocarcinoma (9 of 11 patients), and its mature form was detected in 55% (6 of 11 patients). Immunohistochemistry showed strong and diffuse mesothelin staining in human lung adenocarcinomas and weak or modest staining in squamous cell carcinomas. We detected mesothelin mRNA in 78% of lung cancer cell lines (7 of 9) of the NCI-60 cell line panel. Mesothelin mRNA and proteins were expressed at a high level in non-small cell lung cancer lines EKVX, NCI-H460, NCI-H322M, and NCI-H522. Flow cytometric analysis showed high surface expression of mesothelin in NCI-H322M and EKVX cell lines. Immunotoxin SS1P showed high cytotoxic activity on NCI-H322M and EKVX cells with IC(50) values ranging from 2 to 5 ng/mL.


CONCLUSIONS
Mesothelin is expressed on the surface of most lung adenocarcinoma cells. Immunotoxin SS1P is cytotoxic against mesothelin-expressing lung cancer cell lines and merits evaluation as a new therapeutic agent in treating non-small cell lung cancer.
Ho
Mitchell
M
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Bera
Tapan K
TK
Willingham
Mark C
MC
Onda
Masanori
M
Hassan
Raffit
R
FitzGerald
David
D
Pastan
Ira
I
D000230:Adenocarcinoma / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000187:drug effects; D000090204:Mesothelin; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000911:Antibodies, Monoclonal; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C474515:SS1(dsFv)PE38; D000090204:Mesothelin