Cachexia induced by Walker 256 tumor growth causes rat lymphocyte death

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2005-02, Vol.54 (2), p.179-186
• Main Authors: MARTINS DE LIMA, Thais, RAMOS LIMA, Manuela M, ALMEIDA, Débora C. G, MENDONCA, José Roberto, CURI, Rui
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Antineoplastic agents; Apoptosis; bcl-2-Associated X Protein; bcl-X Protein; Biological and medical sciences; Body Weight; Cachexia - etiology; Cancer; Carcinoma 256, Walker - immunology; Carcinoma 256, Walker - metabolism; Carcinoma 256, Walker - pathology; Caspase 3; Caspases - metabolism; Cell death; Lymphocytes; Lymphocytes - immunology; Lymphocytes - metabolism; Lymphocytes - pathology; Male; Medical sciences; Membrane Potentials; Mitochondria; Original; Pharmacology. Drug treatments; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; Rats, Wistar; Signal transduction; Tumor Cells, Cultured - transplantation; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumors
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-004-0570-4

Death induction by Walker 256 tumor cachexia in non-tumor-infiltrating lymphocytes was investigated. Lymphocytes from cachectic tumor-bearing rats presented a higher proportion of cells with ruptured membranes, indicating necrotic cell death. The cachexia induced by Walker 256 tumor also increased by 3.6-fold the percentage of cells with fragmented DNA, suggestive of apoptotic cell death. The mitochondria involvement was examined by analysis of mitochondria transmembrane potential using rhodamine 123. Lymphocytes from cachectic tumor-bearing rats presented a more pronounced depolarization of mitochondrial transmembrane potential in comparison with cells from the control group. The expression of important proapoptotic (Bcl-xs, Bax, p53, caspase-3) and antiapoptotic genes (Bcl-2 and Bcl-xL) was also altered by tumor cachexia. These results suggest that the immunosuppression induced by Walker 256 tumor cachexia is at least in part a result of lymphocyte death. Evidence was found for the involvement of mitochondria and important proapoptotic genes in the process of lymphocyte death by Walker 256 tumor cachexia.