ABSTRACT
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.
Subject(s)
Killer Cells, Natural/pathology , NK Cell Lectin-Like Receptor Subfamily B/genetics , Neoplasm Regression, Spontaneous/genetics , Sarcoma/genetics , Animals , CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/pathology , Disease Models, Animal , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Neoplasm Regression, Spontaneous/pathology , Rats , Rats, Inbred Lew , Sarcoma/pathologyABSTRACT
BACKGROUND/AIM: Melanoma is a cancer disease with increasing incidence in the Caucasian population. It is often accompanied by spontaneous regression (SR), probably due to high immunogenicity. Understanding of this phenomenon could allow its induction in clinical practice, but detailed study in humans is impossible for ethical reasons. The aim of this study was to determine the role of fibronectin, tenascin C, and MMP-2 in the process of SR. MATERIALS AND METHODS: Time-lapse study of SR was performed in the MeLiM (Melanoma-bearing Libechov Minipig) model. Skin melanomas were taken from 3 weeks to 8 months of age and immunohistochemically processed for fibronectin, tenascin C and matrix metalloproteinase-2 (MMP-2). RESULTS: Expression of all studied proteins increased up to the 10th week of age. Two structurally different areas were distinguishable from the 3rd month of age. MPP-2 expression predominated in areas with melanoma cells, whereas fibronectin and tenascin-C prevailed in the forming fibrous tissue. CONCLUSION: Rebuilding of melanoma into the fibrous tissue during SR was connected with a general rise in fibronectin and tenascin C expression.
Subject(s)
Melanoma/metabolism , Melanoma/pathology , Animals , Disease Models, Animal , Fibronectins/metabolism , Matrix Metalloproteinase 2/metabolism , Swine , Swine, Miniature , Tenascin/metabolismABSTRACT
Spontaneous regression of tumours is a fascinating phenomenon rarely observed in oncological patients. We used a Lewis rat sarcoma model in which subcutaneous tumours developed after inoculation of the R5-28/clone C4 cells. Rats with tumour progression showed splenomegaly and anaemia. Tumour growth was associated with leucocytosis, granulocytosis, decrease in lymphocyte and CD161(+) population in peripheral blood and increase in serum MCP1 concentration. Animals with spontaneous regression of tumours initially showed an increase in white blood cells number and proportion of granulocytes. Between the 42nd and 49th day, however, values of these parameters dropped in correlation with reduction of tumour size. In spontaneously regressed tumours, vascularization was higher and on the contrary, progressive tumours had more necrotic areas with a high number of infiltrating granulocytes. In conclusion, progression and spontaneous regression of tumours in the Lewis rat sarcoma model is associated with distinct changes in populations of blood cells and immune cells which participate in these completely different processes of tumourigenesis.
Subject(s)
Killer Cells, Natural/metabolism , Sarcoma/genetics , Sarcoma/metabolism , Animals , Disease Models, Animal , Disease Progression , Female , Immunohistochemistry , Rats , Rats, Inbred Lew , Sarcoma/pathologyABSTRACT
Tumor models are essential for basic anticancer research and development of novel therapies. In this study, we used a rat sarcoma model in which subcutaneous tumor develops after D6 cell inoculation. The aim of the current study was to analyze changes in haematological parameters, immune cell sub-populations and cytokine profiling during tumor growth, after tumor excision and after second inoculation of D6 cells. Tumor progression was found to be associated with an increased number of leukocytes and increased proportion of CD11b+ cells in peripheral blood. Serum concentration of chemokine (c-c motif) ligand 2, L-selectin and intra cellular adhesion molecule-1 also increased with growing tumor. However, the proportion of CD4+, CD8+ and MHC II+ cells decreased with growth of tumors. After tumor excision, all these parameters returned to pre-inoculation levels and did not change even after a second inoculation of D6 cells. Moreover, absence of secondary tumors after second inoculation of D6 cells gives an insight into development of antitumor immunity stimulated by primary tumor.
