The
metastasis of
tumor cells to bone involves migration, invasion and adhesion to bone. Breast and
prostate cancer cells have predilection for spreading to bone.
Snake venom-derived
arginine-glycine-aspartic acid (RGD)-containing
disintegrins (e.g.
rhodostomin) have been demonstrated to inhibit cell adhesion. Here, we found that
rhodostomin inhibited the adhesion of breast and prostate
carcinoma cells to both unmineralized and mineralized bone extracellular matrices in a dose-dependent manner, without affecting the viability of
tumor cells. In addition,
rhodostomin also inhibited the migration and invasion of breast and prostate
carcinoma cells. It specifically inhibited the binding of
monoclonal antibody (MoAb) 7E3, which recognizes
integrin alphavbeta3, to
tumor cells, but not those of other MoAbs against other
integrin subunits such as alpha2, alpha3, alpha5 and beta1. As
breast cancer cells MDA-MB-231 were locally injected into tibia in nude mice, histological examination of the tibia of control group revealed that most of the cancellous bone had been replaced by the
breast cancer cells after 28 days' inoculation. In contrast, co-administration of
trigramin with
cancer cells markedly inhibited
tumor growth and bone destruction. Taken together,
disintegrins strongly inhibit the adhesion, migration, invasion of
tumor cells and also
tumor growth of human
breast cancer cells in bone as well. Therefore,
disintegrins may be developed as alternate
therapy for bone
metastasis of
cancer cells.