Shifting gene expression profiles during ex vivo culture of renal tumor cells: implications for cancer immunotherapy.
The use of cultured tumor cells rather than original tumor tissue for the preparation of therapeutic cancer vaccines represents an obvious solution to the problem of availability of adequate quantities of autologous tumor. In this study we investigated possible changes in gene expression accompanying the transition of renal cell carcinoma cells from the original tissue to cell populations in culture. In our study we employed cDNA microarray technology to compare the gene expression pattern of ex vivo cultured renal carcinoma cells to that of the original solid tumor tissue from which the cells were derived. Using this approach we detected changes in the expression of many genes mostly related to the cell lines' physiological properties. Some of the products of those genes showing differential expression between tumor-derived cell line and original tumor are known human autoantigens or tumor-associated antigens. Furthermore, analysis of overexpressed genes revealed the presence of several transcripts with restricted normal tissue distribution, representing self-antigens with potential to elicit autoimmunity. Our results suggest that adapting tumor tissue to culture can result in changes in the level of transcripts specific for known antigens and that more information regarding the composition of tumor cells and their byproducts used in vaccine trials is needed before the efficacy and safety of such procedures can truly be determined.
Moschella
Federica
F
Division of Medical Oncology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Catanzaro
Richard P
RP
Bisikirska
Brygida
B
Sawczuk
Ihor S
IS
Papadapoulos
Kyriakos P
KP
Ferrante
Anthony W
AW
McKiernan
James M
JM
Hesdorffer
Charles S
CS
Harris
Paul E
PE
Maffei
Antonella
A
D000222:Adaptation, Physiological / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D018929:Cell Culture Techniques; D015536:Down-Regulation; D020869:Gene Expression Profiling; D006801:Humans; D007167:Immunotherapy; D007680:Kidney Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D020411:Oligonucleotide Array Sequence Analysis; D012334:RNA, Neoplasm / Q000032:analysis / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D012334:RNA, Neoplasm