Abstract
We present the evaluation of inflammatory cytokines in mouse cutaneous melanoma experimental model, as markers of disease evolution. Moreover, to test our experimental model, we have used low doses of dacarbazine (DTIC). C57 BL/6J mouse of both sexes were subjected to experimental cutaneous melanoma and treated with low doses of DTIC. Clinical parameters and serum cytokines were followed during tumor evolution and during DTIC therapy. Cytokine/chemokine pattern was assessed using xMAP technology and the following molecules were quantified: interleukins (IL)-1-beta, IL-6, IL-10, IL-12 (p70), interferon (IFN)-gamma, granulocyte macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-alpha, macrophage inflammatory protein (MIP)-1alpha, monocyte chemoattractant protein (MCP-1), and keratinocyte-derived chemokine (KC). Significant differences were found between normal females and males mice, female mice having a statistically higher serum concentration of IL-1-beta compared to male mice, while males have a significantly higher concentration of MIP-1-alpha. During melanoma evolution in the female group, IL-1-beta, MIP-1-alpha, and KC circulatory levels were found 10-fold increased, while other cytokines doubled their values. In the male mice group, only circulatory KC increased 4 times, while IL-1-beta and TNF-alpha doubled their circulatory values. Various serum cytokines correlated with the disease evolution in cutaneous melanoma mouse model.
Highlights
Cutaneous melanoma, one of the most aggressive human cancers, is a subject of intense research and constant discoveries [1]
Taking into account all the mentioned issues, we have studied in a standard melanoma mouse model the soluble cytokine/chemokine pattern during melanoma progression and during low doses of DTIC therapy
This serum cytokine is elevated during melanoma evolution and in both animal groups, it is reduced upon cytostatic therapy
Summary
One of the most aggressive human cancers, is a subject of intense research and constant discoveries [1]. As in many other types of solid tumors, expresses cells and molecular features of inflammation and an array of inflammatory cytokines that follow this disease. During an acute inflammatory response, innate cells produce mediators that attract and trigger T-helper (Th)1-polarized T lymphocytes, to secrete cytokines with antitumor activity (e.g., interleukin (IL)-2 and interferon (IFN)-gamma). T cells in combination with antitumor-directed B cell-derived factors (e.g., immunoglobulins) activate tumor inhibitory responses by recruited innate immune cells and cytotoxic T lymphocytes (CTLs); all this cell’s army can induce a tumor rejection. When there is a chronic activation of immune response without resolution of the damaged tissue, accumulation of regulatory T (Treg) cells, Th2 cells, and activated B cells is induced; all these cells secrete protumorigenesis factors (e.g., IL-4, IL-6, IL-10, IL-13, and transforming growth factor (TGF)-beta) that enhances protumorigenesis responses in innate immune cells and inactivate CTL cytotoxicity, favoring tumor promotion [3]. The mediators and cellular effectors of inflammation are, on one hand, common to tumor microenvironment and reside in the tumoral site on the other
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