Tumour development and progression involves the expression of oncogenes and
inactivation of tumour suppressor genes, leading to the appearance of mult
iple malignant characteristics. Malignant melanoma cells express different
growth factors and cytokines and their receptors in respective stages of tu
mour progression, which by autocrine and paracrine effects enable them to g
row autonomously and confer competence to metastasis. Autocrine growth fact
ors (bFGF, MGSA/GRO, IL-8 and sometimes IL-6, PDGF-A, IL-10) produced by me
lanoma cells stimulate proliferation of the producing cell itself, while pa
racrine growth factors (for example PDGF, EGF, TGF-beta, IL-1, GM-CSF, IGF-
I, NGF, VEGF) modulate the microenvironment to the benefit of tumour growth
and invasion. Paracrine effects include angiogenesis, stroma formation, mo
dulation of host immune response, activation of proteolytic enzymes, adhesi
on or motility and metastasis formation. Some growth factors have inhibitor
y effects on melanocytes and early lesions (IL-1, IL-6, TGF-beta, OSM, TNF
and IFN) but not on advanced stage melanomas, and in some cases they switch
to autocrine stimulator (IL-6, TGF-beta). Understanding the involvement of
different growth factors and cytokines in the molecular mechanism of melan
oma progression will help to provide an insight into new future therapeutic
approaches for melanoma. (C) 2000 Academic Press.