Most cited article - PubMed ID 18070419
Multiplex analysis of cytokines involved in tumour growth and spontaneous regression in a rat sarcoma model
BACKGROUND/AIM: Spontaneous regression (SR) of tumours is a rare phenomenon not yet fully understood. The aim of this study was to investigate immune cells infiltrating progressive and SR tumours in a Lewis rat sarcoma model. MATERIALS AND METHODS: Rats were subcutaneously inoculated with rat sarcoma R5-28 (clone C4) cells. Developing tumours were obtained on day 42 and cryosections were immunohistochemically processed for detection of immune cells. RESULTS: A high density of granulocytes was found in the necrotic areas of both progressive and SR tumours. CD4+ cells and CD8+ cells were rare and sparsely dispersed in the tumour tissue without clear difference between the two types of tumours. On the contrary, CD161+ cells were abundant and evenly distributed in SR tumours, but these cells were very rare in progressive tumours. CONCLUSION: Based on the differences in number and distribution of the immune cell subpopulations, we believe that natural killer (CD161+) cells play a major role in the destruction of cancer cells during SR of tumours in this Lewis rat model.
- Keywords
- CD161, CD4, CD8, Tumour, immunohistochemistry, spontaneous regression,
- MeSH
- Killer Cells, Natural pathology MeSH
- CD4-Positive T-Lymphocytes pathology MeSH
- CD8-Positive T-Lymphocytes pathology MeSH
- Immunohistochemistry MeSH
- Rats MeSH
- NK Cell Lectin-Like Receptor Subfamily B genetics MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Rats, Inbred Lew MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Sarcoma genetics pathology MeSH
- Neoplasm Regression, Spontaneous genetics pathology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- NK Cell Lectin-Like Receptor Subfamily B MeSH
Establishment of new animal models using selected cell lines with different behaviour is very important for cancer investigations. In this study, we describe three morphologically distinct rat sarcoma clones-C4, C7 and D6-isolated from the R5-28 cell line. Cells of all clones expressed vimentin, fibronectin, laminin, collagen IV and matrix metalloproteinases 2 and 9. However, desmin, cytokeratins 8 and 18, ZO-1 and desmoplakins I and II were not detected. Significant proliferative capacity was documented by proliferating cell nuclear antigen expression and BrdU positivity. Karyotype of the C4, C7 and D6 cells greatly differed from diploid chromosome number of normal rat somatic cells. High expression of three cytokines-monocyte chemoattractant protein 1, tissue inhibitor of metalloproteinases 1 and vascular endothelial growth factor-was observed in all three clones. However, they varied in concentration of chemokines associated with neutrophil migration and activation-cytokine induced neutrophil chemoattractant 2 and lipopolysaccharide induced CXC chemokine. The C4 clone showed spontaneous tumour regression in vivo that was associated with significant changes in lymphocyte subpopulations.
- MeSH
- Clone Cells * MeSH
- Extracellular Matrix Proteins metabolism MeSH
- Karyotyping MeSH
- Rats MeSH
- Cell Line, Tumor MeSH
- Sarcoma genetics metabolism pathology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Extracellular Matrix Proteins MeSH