Related Experiment Videos
In vitro analysis of the melanoma/endothelium interaction increasing the release of soluble intercellular adhesion
1Advanced Immunotherapy Unit, Centro di Riferimento Oncologico, I.N.R.C.C.S., Aviano, Italy.
Abstract:
Melanoma cells constitutively release intercellular adhesion molecule 1 (ICAM-1) as soluble ICAM-1 (sICAM-1), and its levels are elevated in melanoma patients and correlate with disease progression. However, this correlation is not absolute, suggesting that specific characteristics of neoplastic cells and/or ICAM-1-positive non-neoplastic cells may influence the amounts of circulating sICAM-1. In this study, we found a weak correlation (r = 0.55; r2 = 0.3) between sICAM-1 release by 40 metastatic melanomas (36 primary cultures and 4 cell lines), and ICAM-1 expression on neoplastic cells. In addition, melanoma-secreted interleukin-1alpha (IL-1alpha) (1/40) but not vascular endothelial growth factor (VEGF) (29/40), significantly (P < 0.05) up-regulated the shedding of sICAM-1 by human umbilical vein endothelial cells (HUVEC). This was completely abolished by IL-1alpha/beta neutralizing antibodies both at the protein and mRNA level. Altogether, our results suggest that (i) the extent of sICAM-1 release is distinctive for individual melanomas and can be independent of ICAM-1 expression; (ii) tumor endothelia may sustain levels of sICAM-1 in selected melanomas; (iii) melanoma-released VEGF does not affect ICAM-1 expression and sICAM-1 release by HUVEC. Melanoma-derived sICAM-1 inhibits cell-mediated cytotoxicity of melanoma cells; therefore, constitutive levels of sICAM-1 release and IL-1alpha secretion by individual melanomas can differentially influence tumor progression and the clinical effectiveness of cytotoxic-cell-based vaccines.
Insights
Soluble intercellular adhesion molecule 1 (sICAM-1) levels in melanoma patients vary. Melanoma-secreted interleukin-1alpha (IL-1alpha) can increase sICAM-1 shedding by endothelial cells, impacting tumor progression.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Melanoma cells release soluble intercellular adhesion molecule 1 (sICAM-1), with elevated levels correlating to disease progression.
- The correlation between sICAM-1 levels and melanoma progression is not absolute, suggesting other factors influence circulating sICAM-1.
Purpose of the Study:
- To investigate the relationship between sICAM-1 release by metastatic melanomas and ICAM-1 expression on neoplastic cells.
- To determine the role of melanoma-secreted factors, specifically interleukin-1alpha (IL-1alpha) and vascular endothelial growth factor (VEGF), in regulating sICAM-1 shedding by endothelial cells.
- To understand how melanoma-derived sICAM-1 and IL-1alpha secretion influence tumor progression and the efficacy of cell-based therapies.
Main Methods:
- Analysis of sICAM-1 release from 40 metastatic melanoma samples (36 primary cultures, 4 cell lines).
- Assessment of the correlation between sICAM-1 release and ICAM-1 expression on melanoma cells.
- Incubation of human umbilical vein endothelial cells (HUVEC) with melanoma-secreted IL-1alpha and VEGF to measure sICAM-1 shedding.
- Utilized IL-1alpha/beta neutralizing antibodies to assess their impact on sICAM-1 shedding at protein and mRNA levels.
Main Results:
- A weak correlation (r = 0.55) was observed between sICAM-1 release by melanomas and ICAM-1 expression on neoplastic cells.
- Melanoma-secreted IL-1alpha, but not VEGF, significantly upregulated sICAM-1 shedding by HUVEC.
- The IL-1alpha-induced sICAM-1 shedding was abolished by neutralizing antibodies, confirming IL-1alpha's role.
- VEGF secreted by melanoma cells did not affect ICAM-1 expression or sICAM-1 release by HUVEC.
Conclusions:
- Individual melanomas exhibit distinct sICAM-1 release patterns, potentially independent of their ICAM-1 expression.
- Tumor endothelial cells may contribute to sICAM-1 levels in certain melanoma cases through IL-1alpha signaling.
- Melanoma-derived VEGF does not influence ICAM-1 expression or sICAM-1 shedding by endothelial cells.
- Constitutive sICAM-1 release and IL-1alpha secretion by melanomas can differentially impact tumor progression and the effectiveness of cytotoxic cell-based vaccines.