We found that the expression of HLA-DR in these tumors rather coincides with the expression of CXCL-1 and CXCL-8 chemokines, both known to be expressed in tumors that invade early and are related to invasive stages of melanoma.
The effects of IL-1Ra-mediated regression of xenograft growth on angiogenic proteins (IL-8 and VEGF) were evaluated in an IL-1-producing melanoma (SMEL) xenograft model.
Both pretreatment and simultaneous treatment of melanoma cells with IFN-alpha or IFN-beta inhibited the IL-1beta and TNF-alpha up-regulation of IL-8 mRNA levels.
Further studies are needed to determine if CXCL8 is predictive of response and to confirm the functions of these chemokine and cytokine in BRAF-mutant melanoma under BRAF inhibition.
Unstimulated monocyte-conditioned medium was a less potent inducing agent, but still enhanced mRNA expression of interleukin-6, interleukin-8 and melanoma growth stimulating activity/gro alpha.
From our in vitro and in vivo data we suggest that anoxia-induced regulation of IL-8 might be a characteristic feature of aggressive tumor cells, thus indicating that IL-8 might play a critical role for tumor progression in human malignant melanoma.
Through supervised analysis of RNA expression profiles, we identified 82 genes, including TWIST1, HIF1alpha, and IL-8, which correlated with ERK activation across the panel of cell lines and which decreased with pharmacologic inhibition of ERK activity, suggesting that they are ERK transcriptional targets in melanoma.
RA, co-administered with the dsRNA mimicker polyinosinic-polycytidylic acid (poly(I:C)), synergizes to mount a specific response program able to sense dsRNA through the concurrent upregulation of TLR3, the dsRNA helicases melanoma differentiation-associated antigen-5 (MDA-5) and RA-inducible gene-1 (RIG-1), and the dsRNA-activated protein kinase (PKR) expression, leading breast cancer cells to specifically express downstream transcriptional targets of dsRNA sensors, such as interferon-β (IFNβ), interleukin-8 (IL-8), chemokine (C-C motif) ligand 5 (CCL5), and C-X-C motif Chemokine 10 (CXCL10).
The melanoma cell lines showed different growth patterns in the brain, and these differences were associated with differences in expression of the angiogenic factors VEGF-A and IL-8 and the matrix metalloproteinases MMP-2 and MMP-9.
Taken together, these data confirm that CXCL-8 expression plays a critical role in regulating multiple cellular phenotypes associated with melanoma growth and metastasis.
The chemokines, CXC ligand 1 (CXCL1) and CXCL8, but not CXCL5, are highly expressed in most of the melanoma cell lines, suggesting that the constitutive production of chemokines is highly correlated to endogenous NF-kappaB activity.
At present several clinical trials both in melanoma and thyroid cancer are using BRAF-inhibitors with encouraging results, which are derived also from numerous <i>in vitro</i> pre-clinical studies aimed at evaluate the possible modulation of immune-cell density and of specific pro-tumorigenic chemokine secretion (CXCL8 and CCL2) by several BRAF-inhibitors in the context of melanoma and thyroid cancer.