Invasive and noninvasive uveal melanomas have different adhesive properties.
OBJECTIVE
To establish if invasive and noninvasive uveal melanomas have differences in expression of adhesion molecules, and whether their adhesive interactions with the extracellular matrix (ECM) and endothelium vary.


METHODS
Cells from an invasive and noninvasive uveal melanoma cell line and hepatic and dermal microvascular endothelial cells were assessed by flow cytometry for adhesion molecule expression. Tumour cell adhesion to ECM substrates (collagens I and IV, fibronectin, laminin, and vitronectin) and endothelial cells was also investigated using a commercially available assay or a fluorescence-based in vitro assay, respectively. The significance of results comparing cell lines was determined using a Student's t-test, whereby P-values of less than 0.05 were taken as significant.


RESULTS
alpha1- and alpha4-integrins were not expressed by noninvasive cells, but were detected on invasive cells. The invasive cell line also expressed higher levels of other integrins than the noninvasive line. Correspondingly, invasive cells adhered in higher numbers to ECM substrates and endothelial cells, and for the latter, the difference was highly significant (P<0.001). No preference in adhesion of invasive cells for the hepatic endothelium was observed.


CONCLUSIONS
Successful attachment to and migration through the ECM, basement membrane, and endothelium are vital processes involved in malignant progression. Differential expression of alpha1- and alpha4-integrins by invasive and noninvasive cells infers a role for these receptors in invasion, while the ability of invasive cells to adhere more efficiently to the endothelium suggests that this is a critical factor in uveal melanoma invasion.
Woodward
J K L
JK
Academic Unit of Ophthalmology and Orthoptics, Division of Clinical Sciences (S), University of Sheffield, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, UK. j.k.woodward@sheffield.ac.uk
Rennie
I G
IG
Elshaw
S R
SR
Burn
J L
JL
Sisley
K
K
D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D042783:Endothelial Cells / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D005109:Extracellular Matrix / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014604:Uveal Neoplasms / Q000378:metabolism / Q000473:pathology*
D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D039001:Integrin alpha Chains; D009363:Neoplasm Proteins