2-Methoxyestradiol suppresses osteolytic breast cancer tumor progression in vivo

Muzaffer Cicek, Urszula T. Iwaniec, Michael J. Goblirsch, Anne Vrabel, Ming Ruan, Denis R. Clohisy, Russell R. Turner, Merry Jo Oursler

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Abstract

2-Methoxyestradiol (2ME2), a physiologic metabolite of 17β-estradiol (estrogen), has emerged as a promising cancer therapy because of its potent growth-inhibitory and proapoptotic effects on both endothelial and tumor cells. 2ME2 also suppresses osteoclast differentiation and induces apoptosis of mature osteoclasts, and has been shown to effectively repress bone loss in an animal model of postmenopausal osteoporosis. Given these observations, we have examined whether 2ME2 could effectively target metastasis to bone, osteolytic tumors, and soft tissue tumors. A 4T1 murine metastatic breast cancer cell line was generated that stably expressed Far Red fluorescence protein (4T1/Red) to visualize tumor development and metastasis to bone. In an intervention study, 4T1/Red cells were injected into bone marrow of the left femur and the mammary pad. In the latter study, 2ME2 (10, 25, and 50 mg/kg/d) treatment began on the same day as surgery and was continued for the 16-day duration of study. Tumor cell growth and metastasis to bone were monitored and bone volume was determined by micro-computed tomography. 2ME 2 inhibited tumor growth in soft tissue, metastasis to bone, osteolysis, and tumor growth in bone, with maximum effects at 50 mg/kg/d. Furthermore, tumor-induced osteolysis was significantly reduced in mice receiving 2ME2. In vitro, 2ME2 repressed osteoclast number by inducing apoptosis of osteoclast precursors as well as mature osteoclasts. Our data support the conclusion that 2ME2 could be an important new therapy in the arsenal to fight metastatic breast cancer.

Original languageEnglish (US)
Pages (from-to)10106-10111
Number of pages6
JournalCancer Research
Volume67
Issue number21
DOIs
StatePublished - Nov 1 2007

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Breast Neoplasms
Osteoclasts
Bone and Bones
Neoplasms
Neoplasm Metastasis
Osteolysis
Growth
Apoptosis
2-methoxyestradiol
Postmenopausal Osteoporosis
Bone Development
Ambulatory Surgical Procedures
Femur
Estradiol
Estrogens
Breast
Endothelial Cells
Animal Models
Fluorescence
Bone Marrow

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cicek, M., Iwaniec, U. T., Goblirsch, M. J., Vrabel, A., Ruan, M., Clohisy, D. R., ... Oursler, M. J. (2007). 2-Methoxyestradiol suppresses osteolytic breast cancer tumor progression in vivo. Cancer Research, 67(21), 10106-10111. https://doi.org/10.1158/0008-5472.CAN-07-1362

2-Methoxyestradiol suppresses osteolytic breast cancer tumor progression in vivo. / Cicek, Muzaffer; Iwaniec, Urszula T.; Goblirsch, Michael J.; Vrabel, Anne; Ruan, Ming; Clohisy, Denis R.; Turner, Russell R.; Oursler, Merry Jo.

In: Cancer Research, Vol. 67, No. 21, 01.11.2007, p. 10106-10111.

Research output: Contribution to journalArticle

Cicek, M, Iwaniec, UT, Goblirsch, MJ, Vrabel, A, Ruan, M, Clohisy, DR, Turner, RR & Oursler, MJ 2007, '2-Methoxyestradiol suppresses osteolytic breast cancer tumor progression in vivo', Cancer Research, vol. 67, no. 21, pp. 10106-10111. https://doi.org/10.1158/0008-5472.CAN-07-1362
Cicek M, Iwaniec UT, Goblirsch MJ, Vrabel A, Ruan M, Clohisy DR et al. 2-Methoxyestradiol suppresses osteolytic breast cancer tumor progression in vivo. Cancer Research. 2007 Nov 1;67(21):10106-10111. https://doi.org/10.1158/0008-5472.CAN-07-1362
Cicek, Muzaffer ; Iwaniec, Urszula T. ; Goblirsch, Michael J. ; Vrabel, Anne ; Ruan, Ming ; Clohisy, Denis R. ; Turner, Russell R. ; Oursler, Merry Jo. / 2-Methoxyestradiol suppresses osteolytic breast cancer tumor progression in vivo. In: Cancer Research. 2007 ; Vol. 67, No. 21. pp. 10106-10111.
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