The role of folate receptor alpha (FRalpha) in the response of malignant pleural mesothelioma to pemetrexed-containing chemotherapy.
BACKGROUND
The standard treatment of choice for malignant pleural mesothelioma is chemotherapy with pemetrexed and platinum, but the clinical outcome is poor. This study investigates the response to pemetrexed in a panel of eight mesothelioma cell lines and the clinical outcome for patients treated with pemetrexed in relation to folate receptor alpha (FRalpha).


METHODS
Cell lines were treated with pemetrexed to determine the concentration that reduced growth to 50% (GI(50)). FRalpha expression was determined by western blotting and that of FRalpha, reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT) by real-time quantitative RT-PCR. Immunohistochemistry for FRalpha was carried out on 62 paraffin-embedded samples of mesothelioma from patients who were subsequently treated with pemetrexed.


RESULTS
A wide range of GI(50) values was obtained for the cell lines, H2452 cells being the most sensitive (GI(50) 22 nM) and RS5 cells having a GI(50) value greater than 10 microM. No FRalpha protein was detected in any cell line, and there was no relationship between sensitivity and expression of folate transporters. FRalpha was detected in 39% of tumour samples, generally in a small percentage of cells. There was no correlation between the presence of FRalpha and the outcome of pemetrexed treatment, and no significant difference between histological subtypes.


CONCLUSIONS
Response to treatment with pemetrexed does not depend on the presence of FRalpha.
Nutt
J E
JE
Northern Institute for Cancer Research, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
Razak
A R A
AR
O'Toole
K
K
Black
F
F
Quinn
A E
AE
Calvert
A H
AH
Plummer
E R
ER
Lunec
J
J
D015153:Blotting, Western; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D058973:Folate Receptors, GPI-Anchored; D005493:Folic Acid Antagonists / Q000627:therapeutic use*; D005971:Glutamates / Q000627:therapeutic use*; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D008654:Mesothelioma / Q000188:drug therapy*; D000068437:Pemetrexed; D010997:Pleural Neoplasms / Q000188:drug therapy*; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D005493:Folic Acid Antagonists; D005971:Glutamates; D011956:Receptors, Cell Surface; D000068437:Pemetrexed; D006147:Guanine