Integrins mediate cell adhesion to the extracellular matrix.
Integrin alphavbeta3 recognizes the RGD motif as a
ligand-binding site and has been associated with high malignant potential in
breast cancer cells, signaling the onset of widespread
metastasis. In recent years, several antagonists of
integrin alphavbeta3, including RGD
peptides, have been used as potential anti-
cancer agents. In the present work, the effect of the linear RGD hexapeptide
GRGDSP was studied, for the first time, on
breast tumor explants, as well as on well-spread human
breast cancer cells from primary cultures, using the explant technique, to clarify the role of this
peptide in the suppression of
breast cancer cell migration. The results showed that incubation of
breast tumor explants with
RGD peptide at the beginning of culture development inhibited completely the migration of
cancer cells out of the tissue fragment as revealed by electron microscopy. RGD incubation of well-spread
breast cancer cells from primary culture resulted in rounding and shrinkage of the cells accompanied by altered distribution of
integrin alphavbeta3 and concomitant
F-actin cytoskeletal disorganization, as revealed by immunofluorescence. Electron immunocytochemistry showed aggregation of
integrin alphavbeta3 at the cell periphery and its detection in noncoated vesicles. However, Western immunoblotting showed no change in beta3 subunit expression, despite the altered distribution of the
integrin alphavbeta3. In light of the above, it appears that the
RGD peptide plays an important role in the modulation of cell motility and in the perturbation of cell attachment affecting the malignant potential of
breast cancer cells in primary cultures.