Transcriptional response of peripheral lymphocytes to early fibrosarcoma: a model system for cancer detection based on hybridization signatures.
Since circulating leukocytes, mainly B and T cells, continuously maintain vigilant and comprehensive immune surveillance, these cells could be used as reporters for signs of infection or other pathologies, including cancer. Activated lymphocyte clones trigger a sensitive transcriptional response, which could be identified by gene expression profiling. To assess this hypothesis, we conducted microarray analysis of the gene expression profile of lymphocytes isolated from immunocompetent BALB/c mice subcutaneously injected with different numbers of tumorigenic B61 fibrosarcoma cells. Flow cytometry demonstrated that the number of circulating T (CD3(+)CD4(+) or CD3(+)CD8(+)) or B (CD19(+)) cells did not change. However, the lymphocytes isolated from tumor cell-injected animals expressed a unique transcriptional profile that was identifiable before the development of a palpable tumor mass. This finding demonstrates that the transcriptional response appears before alterations in the main lymphocyte subsets and that the gene expression profile of peripheral lymphocytes can serve as a sensitive and accurate method for the early detection of cancer.
Molecular Immunogenetics Group, Department of Genetics, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), 14040-900, Ribeirão Preto, SP, Brazil.
Márcia M C
MM
Marques
Cristina M
CM
Junta
Carlos R
CR
Zárate-Blades
Elza Tiemi
ET
Sakamoto-Hojo
Eduardo A
EA
Donadi
Geraldo A S
GA
Passos
D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D005260:Female; D005354:Fibrosarcoma / Q000175:diagnosis* / Q000473:pathology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D006824:Hybridization, Genetic / Q000502:physiology*; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic / Q000502:physiology*
D018941:Antigens, CD19; D011065:Poly(ADP-ribose) Polymerases; C459820:Parp2 protein, mouse; C495902:Cdk4 protein, mouse; D051358:Cyclin-Dependent Kinase 4; D000243:Adenosine Deaminase