BISPHOSPHONATES INHIBIT THE ADHESION OF BREAST-CANCER CELLS TO BONE MATRICES IN-VITRO

Bisphosphonates are used with increasing frequency in the management o f skeletal complications in patients with breast cancer, In this paper , we have investigated whether bisphosphonates, besides their known be neficial effects on tumor-associated osteoclastic resorption, are capa ble of inhibiting breast cancer cell adhesion to bone matrix, For that we used two in vitro models for bone matrix (cortical bone slices and cryostat sections of trabecular bone from neonatal mouse tails). Four bone matrix-bound nitrogen-containing bisphosphonates (pamidronate, o lpadronate, alendronate, and ibandronate) inhibited adhesion and sprea ding of breast cancer cells to bone dose-dependently, whereas etidrona te and clodronate had little or no effect, Strikingly, the relative or der of potency of the bisphosphonates in inhibiting the adhesion of ca ncer cells to cortical and trabecular bone corresponded to their relat ive antiresorptive potencies in vivo as well as their ranking in in vi tro bone resorption assays with predictive value for their clinical ef ficacy. It appears that nitrogen-containing bisphosphonates alter sele ctively the adhesive properties of the extracellular bone matrix preve nting the attachment of breast cancer cells to it. Besides the benefic ial effects of bisphosphonates on tumor-induced osteoclastic resorptio n, the previously unrecognized effect presented in this paper makes th ese agents suitable for earlier pharmacologic intervention in patients with breast cancer at risk of developing bone metastases.