In Vivo human melanoma cytokine production: Inverse correlation of GM‐CSF production with tumor depth

Abstract

Melanomas produce multiple cytokines which may influence their growth in vivo. Experimental evidence suggests that granulocyte macrophage-colony stimulating factor (GM-CSF) can induce a potent anti-melanoma response. whereas interleukin-8 (IL-8) may act as a growth factor in human melanoma. Little is currently known regarding the production of these cytokines by human melanoma in vivo. In this study we tested the hypothesis that endogenous production of GM-CSF and IL-8 can be correlated with the depth of human malignant melanoma surgical specimens. We examined 45 melanocytic human tissue samples consisting of 27 primary cutaneous melanomas, 9 metastatic melanomas, and 9 dysplastic nevi for in vivo GM-CSF and IL-8 production using immunohistochemistry. The majority of thin melanomas (< or = 0.76 mm) stained highly positive for GM-CSF with little or no staining for IL-8 whereas the medium (>0.76- < or = 4.0 mm) and thick (>4.0 mm) melanoma specimens showed little or no staining for GM-CSF and significant amounts of IL-8 staining. Metastatic melanoma as well as dysplastic nevi specimens had little or no GM-CSF and IL-8 staining. These results support the hypothesis that endogenous melanoma cytokines such as GM-CSF and IL-8 with opposing effects on tumor progression play an important role in melanoma growth and regulation.

CXCL8 and Its Cognate Receptors in Melanoma Progression and Metastasis

“…Interestingly, an intense CXCL8 immuno-reactivity was observed in the metastatic lesions from skin, muscle and lymph node [8,9]. Similar results have been demonstrated in another study showing a correlation between CXCL8 expression and tumor depth [40]. These data suggest an association between the expression of CXCL8 and metastasis in human cutaneous melanoma.…”

Breast Cancer Cell–Derived GM-CSF Licenses Regulatory Th2 Induction by Plasmacytoid Predendritic Cells in Aggressive Disease Subtypes

“…Previous studies have shown the presence of GM-CSF in diverse type of tumors, including breast cancer (17,(44)(45)(46)(47). GM-CSF can function as an immune adjuvant by activating NK cells and myeloid cells (48), and is widely used in antitumor therapy (49,50).…”

Correlation of IL-8 with induction, progression and metastatic potential of colorectal cancer

“…For example, various recent studies point out that IL-8 expression correlates with disease progression in human melanoma [17][18][19] . On the other hand, IL-8 expression in melanoma is only associated with early malignancy, whereas metastatic melanoma as well as dysplastic naevi specimens showed little or no IL-8 upregulation as shown by immunohistochemical staining [20] . Although constitutive IL-8 expression was determined in melanoma cells from surgical specimens, no correlation was found between the degree of cytokine expression and the clinical tumor stage [21] .…”