Claudin 7 as a possible novel molecular target for the treatment of pancreatic cancer.

BACKGROUND/OBJECTIVES: Pancreatic cancer consists of various subpopulations of cells, some of which have aggressive proliferative properties. The molecules responsible for the aggressive proliferation of pancreatic cancer may become molecular targets for the therapies against pancreatic cancer. METHODS: From a human pancreatic cancer cell line, MIA PaCa-2, MIA PaCa-2-A cells with an epithelial morphology and MIA PaCa-2-R cells with a non-epithelial morphology were clonogenically isolated by the limiting dilution method. Gene expression of these subpopulations was analyzed by DNA microarray. Gene knockdown was performed using siRNA. RESULTS: Although the MIA PaCa-2-A and MIA PaCa-2-R cells displayed the same DNA short tandem repeat (STR) pattern identical to that of the parental MIA PaCa-2 cells, the MIA PaCa-2-A cells were more proliferative than the MIA PaCa-2-R cells both in culture and in tumor xenografts generated in immunodeficient mice. Furthermore, the MIA PaCa-2-A cells were more resistant to gemcitabine than the MIA PaCa-2-R cells. DNA microarray analysis revealed a high expression of claudin (CLDN) 7 in the MIA PaCa-2-A cells, as opposed to a low expression in the MIA PaCa-2-R cells. The knockdown of CLDN7 in the MIA PaCa-2-A cells induced a marked inhibition of proliferation. The MIA PaCa-2-A cells in which CLDN7 was knocked down exhibited a decreased expression of phosphorylated extracellular signal-regulated kinase (p-Erk)1/2 and G1 cell cycle arrest. CONCLUSIONS: CLDN7 may be expressed in the rapidly proliferating and dominant cell population in human pancreatic cancer tissues and may be a novel molecular target for the treatment of pancreatic cancer.

Identification of HLA class I-binding peptides derived from unique cancer-associated proteins by mass spectrometric analysis.

BACKGROUND/AIM: Since antigenic peptides of the cancer-associated antigens presented on human leukocyte antigen (HLA) molecules are recognized by specific cytotoxic T-lymphocytes, they have the potential to becoming effective peptide vaccines for cancer immunotherapy. MATERIALS AND METHODS: Peptides binding to HLA-A*0201 and HLA-A*2402 obtained from human prostate cancer cells by acid-elution were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and source proteins of the peptides were determined based on the HLA-binding capacity listed on the Syfpeithi. RESULTS: We identified TKLSA possibly derived from absent in melanoma 1-like protein (AIM1L), and RLRYT from trans-membrane protein-191C (TMEM 191C) or c20orf201. Messenger RNAs encoding these proteins were expressed in various cancer cell types but none or very few in non-cancerous tissues except for testis, cerebellum and ovary. CONCLUSION: HLA class I-binding peptides of unique cancer-associated proteins were identified by MS analysis, and might become a promising tool for the generation of novel cancer vaccines.