Stimulation and inhibition of uveal melanoma invasion by HGF, GRO, IL-1alpha and TGF-beta.
OBJECTIVE
To investigate potential factors involved in uveal melanoma migration and invasion in vitro.


METHODS
Using a microchemotaxis chamber, the effects were studied of a range of stimulators and inhibitors on a series of 10 primary uveal melanomas and 2 uveal melanoma cell lines, by assessing invasion through an 8- micro m pore membrane, precoated with an extracellular matrix solution. In addition, invasion in response to the effect of cells and conditioned media derived from the liver and other tissues was studied for one uveal melanoma culture, by using double-chambered wells, and invasion was assessed through an 8- micro m pore membrane, precoated with synthetic extracellular matrix. In all instances, invading cells were counted under x400 magnification on the lower surface of the membrane. Levels of invasion were correlated with histopathologic markers of prognosis.


RESULTS
Conditioned media and cells derived from other tissues, including the liver, increased cellular invasion of the uveal melanoma cell line studied. For specific regulators, maximum stimulation of invasion was induced by hepatic growth factor (HGF), growth-related oncogene (GRO), and macrophage inflammatory protein (MIP)-1beta, whereas significant inhibition was induced by IL-1alpha, TGF-beta1, and TGF-beta2.


CONCLUSIONS
The primary site of metastasis in patients with uveal melanoma is the liver. For the degree of site specificity commonly seen, regulators involved in the process may be expressed at the secondary sites, promoting adhesion, migration, invasion, and proliferation of tumor cells. HGF, GRO, MIP-1beta, IL-1alpha, TGF-beta1, and TGF-beta2 may play a significant role in regulating invasion of uveal melanoma cells.
D000368:Aged; D000369:Aged, 80 and over; D054407:Chemokine CCL4; D054360:Chemokine CXCL1; D018925:Chemokines / Q000494:pharmacology*; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000494:pharmacology*; D005260:Female; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008297:Male; D008545:Melanoma / Q000473:pathology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014604:Uveal Neoplasms / Q000473:pathology*
C475829:CXCL1 protein, human; D054407:Chemokine CCL4; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D019402:Macrophage Inflammatory Proteins; D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor