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Breast Cancer Research
Published in: Breast Cancer Research 1/2001

01-02-2001 | Review

The role of bisphosphonates in breast cancer: Direct effects of bisphosphonates on breast cancer cells

Authors: Siddhika G Senaratne, Kay W Colston

Published in: Breast Cancer Research | Issue 1/2001

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Abstract

In addition to inhibiting bone resorption, bisphosphonates have also been shown to exhibit antitumour effects. In vitro, bisphosphonates inhibit proliferation and induce apoptosis in cultured human breast cancer cells. In addition, bisphosphonate treatment interferes with breast cancer cell adhesion to bone matrix, and inhibits cell migration and invasion. The combination of bisphosphonates with other anticancer drugs such as the taxoids markedly enhances these effects. These newly recognized direct actions of bisphosphonates on breast cancer cells indicate that these agents may have a greater role to play in treatment of patients suffering from cancers with a propensity to metastasize to bone.
Literature
1.
Elte JWF, Bijovoet OLM, Cleton FJ, van Oosterom AT, Sleeboom HP: Osteolytic metastases in breast carcinoma. Pathogenesis, morbidity and bisphosphonates treatment. Eur J Cancer Oncol. 1986, 22: 493-500.CrossRef
2.
Paterson AHG: Bone metastases in breast cancer, prostate cancer and myeloma. Bone. 1987, 8(suppl 1): S17-S22.
3.
4.
Mundy GR: Mechanism of osteolytic bone destruction. Bone. 1991, 12(suppl 1): S1-S6.CrossRef
5.
Lipton A, Theriault RL, Hortobagyi GN, Simeone J, Knight RD, Mellars K, Reitsma DJ, Heffernan M, Seaman JJ: Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-control trials. Cancer. 2000, 88: 1082-1090. 10.1002/(SICI)1097-0142(20000301)88:5<1082::AID-CNCR20>3.3.CO;2-Q.CrossRefPubMed
6.
Boonekamp PM, van der Wee-Pals LJ, van Wijk-van Lennep MML, Thesing CW, Bijvoet OL: Two modes of action of bisphosphonates on osteoclastic resorption of mineralized matrix. J Bone Miner. 1986, 1: 27-39.
7.
Ryzen E, Martodam R, Troxell M, Benson A, Paterson A, Shepard K, Hicks R: Intravenous etidronate in the management of malignant hypercalcaemia. Arch Intern Med. 1985, 145: 449-452. 10.1001/archinte.145.3.449.CrossRefPubMed
8.
Kanis JA, Urwin GH, Gray RE, Beneton MN, MvCloskey EV, Hamdy NA, Murray SA: Effects of intravenous etidronate on skeletal and calcium metabolism. Am J Med. 1987, 82: 55-70.CrossRefPubMed
9.
Lowik CWGM, van der Pluijm G, van der Wee-Pals LJA, Bloys van Trsiong-de Groot H, Bijvoet OLM: Migration and phenotypic transformation of osteoclasts precursors into mature osteoclasts: the effect of a bisphosphonate. J Bone Miner Res. 1988, 3: 185-192.CrossRefPubMed
10.
Hughes DE, MacDonald BR, Russell RGG, Gowen M: Inhibition of osteoclast-like cell formation by bisphosphonates in long term cultures of human bone marrow. J Clin Invest. 1989, 83: 1930-1935.CrossRefPubMedPubMedCentral
11.
Hughes DE, Wright KR, Uy HL, Sasaki A, Yoneda T, Toodman GD, Mundy GR, Boyce BF: Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res. 1995, 10: 1478-1487.CrossRefPubMed
12.
Selander KS, Monkkonen J, Karhukorpi E, Harkonen P, Hannuniemi R, Vaananen KK: Characteristics of clodronate-induced apoptosis in osteoclasts and macrophages. Mol Pharmacol. 1996, 50: 1127-1138.PubMed
13.
Sasaki A, Boyce BF, Story B, Wright KR, Chapman M, Boyce R, Mundy GR, Yoneda T: Bisphosphonate risedronate reduces metastatic human breast cancer burden in bone in nude mice. Cancer Res. 1995, 55: 3551-3557.PubMed
14.
Yoneda T, Sasaki A, Dustan C, William PJ, Bauss F, De Clerck YA, Mundy GR: Inhibition of osteolytic bone metastasis of breast cancer by combined treatment with the bisphosphonates ibandronate and tissue inhibitor of the matrix metalloproteinase-2. J Clin Invest. 1997, 99: 2509-2517.CrossRefPubMedPubMedCentral
15.
Colucci S, Minielli V, Zambonin G, Grno M: Alendronate acts on bone resorption of human osteoclast-like cells through the inhibition of cell attachment to bone surfaces [abstract]. Bone. 1995, 17: 599-10.1016/8756-3282(96)87948-8.CrossRef
16.
van der Pluijm G, Vloedgraven H, van Beek E, van der Wee, Lowik C, Papapoulos SJ: Bisphosphonates inhibit the adhesion of breast cancer cells to bone matrices in vitro. Clin Invest. 1996, 98: 698-705.CrossRef
17.
Boissier S, Magnetto S, Frappart L, Cuzin B, Ebetino FH, Delmas PD, Clezardin P: Bisphosphonates inhibit prostate and breast carcinoma cell adhesion to unmineralized and mineralized bone extracellular matrices. Cancer Res. 1997, 57: 3890-3894.PubMed
18.
Magnetto S, Boissier S, Delmas PD, Clezardin P: Additive antitu-mour activities of taxoids in combination with the bisphosphonate ibandronate against invasion and adhesion of human breast carcinoma cells to bone. Int J Cancer. 1999, 83: 263-269. 10.1002/(SICI)1097-0215(19991008)83:2<263::AID-IJC19>3.0.CO;2-T.CrossRefPubMed
19.
Boissier S, Ferreras M, Peyruchaud O, Magnetto S, Ebetino FH, Colombel M, Delmas P, Delaisse J-M, Clezardin P: Bisphosphonates inhibit breast and prostate carcinoma cell invasion, an early event in the formation of bone metastases. Cancer Res. 2000, 60: 2949-2954.PubMed
20.
Hiraga T, Tanaka S, Yamamoto M, Nakajima T, Ozawa H: Inhibitory effects of bisphosphonate (YM175) on bone resorption induced by a metastatic bone tumour. Bone. 1996, 18: 1-7. 10.1016/8756-3282(95)00428-9.CrossRefPubMed
21.
Shipman CM, Rogers MJ, Apperley JF, Russell RGG, Croucher PI: Bisphosphonate induced apoptosis of human myeloma cell lines: a novel antitumour activity. Br J Haematol. 1997, 98: 665-672. 10.1046/j.1365-2141.1997.2713086.x.CrossRefPubMed
22.
Diel IJ, Solomayer EF, Costa SD, Gollan C, Goerner R, Wallwiener D, Kaufmann M, Bastert G: Reduction in new metastases in breast cancer with adjuvant clodronate treatment. N Engl J Med. 1998, 339: 357-363. 10.1056/NEJM199808063390601.CrossRefPubMed
23.
Senaratne SG, Pirianov G, Mansi JL, Arnett TR, Colston KW: Bisphosphonates induce apoptosis in human breast cancer cell lines. Br J Cancer. 2000, 82: 1459-1468.CrossRefPubMedPubMedCentral
24.
Busch M, Rave-Frank M, Hille A, Duhmke E: Influence of clo-dronate on breast cancer cells in vitro. Eur J Med Res. 1998, 3: 427-431.PubMed
25.
Fleisch H: Bisphosphonates in bone disease, 3rd ed. New York: Parthenon Publishing Group;. 1997
26.
Fromigue O, Lagneaux L, Body JJ: Bisphosphonates induce breast cancer cell death in vitro. J Bone Miner Res. 2000, 15: 2211-2221.CrossRefPubMed
27.
Senaratne SG, Colston KW: Mechanisms involved in aminobis-phosphonate-induced apoptosis in breast cancer cells [abstract]. Proc Am Assoc Cancer Res. 2001, 42: 2377-
28.
Hiraga T, Williams PJ, Mundy GR, Yoneda T: The bisphosphonate Ibandronate promotes apoptosis in MDA-MB-231 human breast cancer cells in bone metastases. Cancer Res. 2001, 61: 4418-4424.PubMed
29.
Jagdev SP, Coleman RE, Shipman CM, Rostami HA, Croucher PI: The bisphosphonate, zoledronic acid, induces apoptosis of breast cancer cells: evidence for synergy with paclitaxel. Br J Cancer. 2001, 84: 1126-1134. 10.1054/bjoc.2001.1727.CrossRefPubMedPubMedCentral
30.
Luckman SP, Coxon FP, Ebetino FH, Russell RGG, Rogers MJ: Heterocycle-containing bisphosphonates causes apoptosis and inhibit bone resorption by preventing protein prenylation: evidence from structure-activity relationships in J774 macrophages. J Bone Miner Res. 1998, 13: 1668-1678.CrossRefPubMed
31.
Shipman CM, Croucher PI, Russell RGG, Helfrich MH, Rogers MJ: The bisphosphonates incadronate (YM175) causes apoptosis of human myeloma cells in vitro by inhibiting the mevalonate pathway. Cancer Res. 1998, 58: 5294-5297.PubMed
32.
Sato M, Gransser W, Endo N, Akins R, Simmons H, Thompson DD, Golub E, Rodan GA: Bisphosphonates action. Alendronate localization in rat bone and effects on osteoclast ultrastructure. J Clin Invest. 1991, 88: 2095-2105.CrossRefPubMedPubMedCentral
Metadata
Title
The role of bisphosphonates in breast cancer: Direct effects of bisphosphonates on breast cancer cells
Authors
Siddhika G Senaratne
Kay W Colston
Publication date
01-02-2001
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2001
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr412

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