Bisphosphonates inhibit the adhesion of breast cancer cells to bone matrices in vitro.
Bisphosphonates are used with increasing frequency in the management of skeletal complications in patients with breast cancer. In this paper, we have investigated whether bisphosphonates, besides their known beneficial effects on tumor-associated osteoclastic resorption, are capable 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, olpadronate, alendronate, and ibandronate) inhibited adhesion and spreading of breast cancer cells to bone dose-dependently, whereas etidronate and clodronate had little or no effect. Strikingly, the relative order of potency of the bisphosphonates in inhibiting the adhesion of cancer cells to cortical and trabecular bone corresponded to their relative antiresorptive potencies in vivo as well as their ranking in in vitro bone resorption assays with predictive value for their clinical efficacy. It appears that nitrogen-containing bisphosphonates alter selectively the adhesive properties of the extracellular bone matrix preventing the attachment of breast cancer cells to it. Besides the beneficial effects of bisphosphonates on tumor-induced osteoclastic resorption, the previously unrecognized effect presented in this paper makes these agents suitable for earlier pharmacologic intervention in patients with breast cancer at risk of developing bone metastases.
van der Pluijm
G
G
Department of Endocrinology and Metabolic Diseases, University Hospital, Leiden, The Netherlands. pluijm@rullf2.leidenuniv.nl
Vloedgraven
H
H
van Beek
E
E
van der Wee-Pals
L
L
Löwik
C
C
Papapoulos
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001857:Bone Matrix / Q000473:pathology*; D001859:Bone Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology*; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D008875:Middle Aged; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004164:Diphosphonates