Interleukin-6 undergoes transition from paracrine growth inhibitor to autocrine stimulator during human melanoma progression.

Abstract

Abstract. The ability to penetrate the dermal basement membrane and subsequently proliferate in the underlying mesenchyme is one of the key steps in malignant progression of human melanomas. We previously undertook studies aimed at assessing how normal dermal fibroblasts (one of the main cellular components of mesenchyme) may affect the growth of human melanoma cells and facilitate the overgrowth of malignant subpopulations (Comil, I., D. Theodorescu, S. Man, M. Herlyn, J. Jambrosic, and R. S. Kerbel. 1991. Proc. Natl. Acad. Sci. USA. 88:6028-6032). We found that melanoma cell lines from early-stage (metastatically incompetent) lesions were growth inhibited whereas those from advanced-stage (metastatically competent) lesions were stimulated under the same conditions by co-culture with fibroblasts; conditioned medium from such cells gave the same result.

Diagnosing melanoma patients entering American Joint Committee on Cancer stage IV, C-reactive protein in serum is superior to lactate dehydrogenase

“…As a nonspecific acute phase response to almost all forms of inflammation (Pepys, 1995), CRP is synthesised in hepatocytes in response to cytokines such as mainly interleukin-6 (Il-6; Moshage et al, 1988;Castell et al, 1989;Kishimoto, 1989;Klein et al, 1991;Hirano, 1992). As melanoma cells are known to produce Il-6 (Colombo et al, 1992;Lee et al, 1992;Lu and Kerbel 1993;Mattei et al, 1994;Francis et al, 1996), serum CRP might reflect Il-6 production from the tumour. However, tumour-specific immune interaction with T cells, macrophages or monocytes might also be responsible for elevated Il-6 levels, as these cell are known to produce this cytokine, too.…”

Prognostic value of serum levels of interleukin 6 and of serum and plasma levels of vascular endothelial growth factor in hormone-refractory metastatic breast cancer patients

“…Finally, IL-6 promotes osteoclast formation and inhibits dendritic cell differentiation, thus facilitating metastatic growth (Menetrier-Caux et al, 1998;Grano et al, 2000). As tumours evolve toward a metastatic phenotype and interfere with other endogenous or exogenous factors, IL-6 activity on cancer cells and their environment might actually shift from growth inhibition and differentiation to proliferation and antiapoptosis (Lu and Kerbel, 1993;Chiu et al, 1996;Badache and Hynes, 2001). This could explain the favourable prognosis associated with the presence of tumour IL-6 in early-stage breast cancer (Karczewska et al, 2000) and the poor survival associated with high serum IL-6 levels in this series of metastatic breast cancer patients.…”

Serum interleukin 6 and C-reactive protein levels correlate with resistance to IL-2 therapy and poor survival in melanoma patients

“…These resistance phenomena were often associated with spontaneous IL-6 secretion by these advanced-stage cell lines (Lu et al, 1993). Therefore, this multicytokine resistance phenotype may explain the failure of IL-2 therapy in such patients, if IL-2 acts by inducing selective cytokines or inhibitory factors.…”