G. Vanderpluijm et al., BISPHOSPHONATES INHIBIT THE ADHESION OF BREAST-CANCER CELLS TO BONE MATRICES IN-VITRO, The Journal of clinical investigation, 98(3), 1996, pp. 698-705
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.