Differential profiling analysis of proteins involved in anti-proliferative effect of interferon-alpha on renal cell carcinoma cell lines by protein biochip technology.
Interferon-alpha (IFN) is widely used for the treatment of progressive renal cell carcinoma (RCC), but its effective response rate is only about 15%. New biomarkers of RCC contributing to the effective IFN treatment are needed to establish a sensitivity test for evaluating if the IFN is effective or not against RCC. All the proteins expressed in the IFN-susceptible and -resistant RCC cell lysates were analyzed by surface enhanced laser desorption ionization (SELDI) mass spectrometry using ProteinChip technology and their different protein expression were detected by the comparison of the profiles between them. We detected the following candidate markers that exhibited peak shifts: a) in the IFN-susceptible cell lines, a candidate marker with a molecular weight of 5,688 Da was detected on a hydrophobic (H4) chip: b) in the IFN-resistant cell lines, candidate markers each with a molecular weight of 8,049, 3,157, 3,993, and 8,959 Da were detected on strong anion exchange (SAX2, pH 9.0, two types) chips, H4 chip, and weak cation exchange (WCX, pH 9.0) chips, respectively. IFN treatment produced no weight increase in these four proteins, and c) candidate marker with a molecular weight of 1,623 Da that was expressed in both cell lines after the IFN treatment was detected on the H4 chip. These data suggest that the ProteinChip system is very useful in identifying proteins showing unique peaks in the RCC cell lines with different IFN susceptibility, and the comparison of these proteins measured in RCC cell lysates may help to identify the IFN sensitivity. Furthermore, the discovery of a susceptibility and or a inhibitory factor may eventually lead to the development of a novel drug targeting the respective factor for the improvement of anticancer chemotherapy.
Nakamura
Kogenta
K
Department of Urology, Aichi Medical University School of Medicine, Aichi 480-1195, Japan.
Yoshikawa
Kazuhiro
K
Yamada
Yoshiaki
Y
Saga
Shinsuke
S
Aoki
Shigeyuki
S
Taki
Tomohiro
T
Tobiume
Motoi
M
Shimazui
Toru
T
Akaza
Hideyuki
H
Honda
Nobuaki
N
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002457:Cell Extracts / Q000737:chemistry; D045744:Cell Line, Tumor; D030562:Databases, Protein; D019008:Drug Resistance, Neoplasm; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D040081:Protein Array Analysis / Q000379:methods; D011506:Proteins / Q000032:analysis* / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
D000970:Antineoplastic Agents; D002457:Cell Extracts; D016898:Interferon-alpha; D011506:Proteins