Zoledronic Acid Inhibits the Motility of Cancer Stem-like Cells from the Human Breast Cancer Cell Line MDA-MB 231.
OBJECTIVE
Various effects on tumor cells have been described for zoledronic acid (ZOL). However, only limited data exist regarding its influence on the motility of tumor cells. Since migration of tumor stem cells is a decisive step in metastasis, we examined whether ZOL reduces their motility.


METHODS
We investigated the effects of ZOL on stem-like progenitor cells obtained via the formation of spheroids from the human breast cancer cell line MDA-MB 231. Stem cell properties were verified by measurement of high CD44 expression and absence of CD24 expression. Motility was explored by time-resolved videography, protein expression by western blotting.


RESULTS
ZOL strongly reduced the migration of stem-like progenitor cells. Cellular velocity was reduced by 61% following exposure to 1 μM ZOL and by 82% after exposure to 10 μM ZOL. Accumulated distance traveled by the cells was reduced by 60% and 79% after exposure to 1 μM and 10 μM ZOL, respectively. The remaining cellular motility led to very little change in distance, with cellular activity appearing more as "stepping on the spot". The reduced motility might be due to reduced phosphorylation of focal adhesion kinase (FAK), an important enzyme in cellular migration.


CONCLUSIONS
ZOL reduces the motility and cellular velocity of breast cancer cells in vitro. The reduced mobility might slow down or even stop metastasis, which is a known result of adjuvant ZOL therapy in breast cancer patients. In vivo studies are warranted to evaluate the impact of the reduced motility on the metastatic cascade.
Institute for Radiation Biology, Department of Radiation Oncology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany helmut.buehler@elisabethgruppe.de.
Helmut
H
Bühler
Institute for Radiation Biology, Department of Radiation Oncology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany.
Clemens
C
Hoberg
Institute for Radiation Biology, Department of Radiation Oncology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany.|Department of Radiation Oncology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany.
Khashayar
K
Fakhrian
Institute for Radiation Biology, Department of Radiation Oncology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany.|Department of Radiation Oncology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany.
Irenäus A
IA
Adamietz
D050071:Bone Density Conservation Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D051927:CD24 Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism; D059008:Time-Lapse Imaging / Q000379:methods; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D051927:CD24 Antigen; D004164:Diphosphonates; D018960:Hyaluronan Receptors; D007093:Imidazoles; D000077211:Zoledronic Acid; D051416:Focal Adhesion Protein-Tyrosine Kinases
Breast cancer stem cells; breast cancer metastasis; motility; tumor cell migration; zoledronic acid