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In Vivo Inhibition of Bone Morphogenetic Protein-2 on Breast Cancer Cell Growth

Ye, Shuai, MS*; Park, Byung-Hyun, MD; Song, Kyung-Jin, MD*; Kim, Jung-Ryul, MD*; Jang, Kyu-Yun, MD; Park, Ho-Sung, MD; Bae, Jun Sang, MS; Brochmann, Elsa J., PhD‖,**; Wang, Jeffrey C., MD¶,††; Murray, Samuel S., MD‖,**,††; Lee, Kwang-Bok, MD, PhD*,§

doi: 10.1097/BRS.0b013e31827db4c6
Basic Science
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Study Design. In vitro and in vivo study.

Objective. To evaluate the role of recombinant human bone morphogenetic protein-2 (rhBMP2) on breast cancer cell (MDA-MB-231 cells) growth.

Summary of Background Data. Bone morphogenetic proteins (BMPs) are expressed in a variety of human carcinoma cell lines and are known to promote tumor invasion and metastasis. However, their roles in tumor progression have not been fully clarified. In addition, there is no in vivo study regarding the inhibitory effect of BMP2 on breast cancer cell proliferation.

Method. Cell proliferation was determined by BrdU incorporation assay and flow cytometry. BMP2 signal transduction pathways were estimated on Western blot. Fifteen animals were divided into 2 groups; 1 (control = 5) was breast cancer cells alone, while the other (experiment = 5) was rhBMP2 + breast cancer cells. Cancer cells were injected into 2 sites (subcutaneous and femur) of nude mice with or without BMP2. Tumor size was determined by direct measurements for subcutaneous tumor formation and by femur radiographs. Histological and immunohistochemical analyses were performed.

Results. RhBMP2 inhibited the proliferation of MDA-MB-231 cells in vitro. Inhibition was associated with changes in both the Smad and Wnt signaling pathways and was ultimately mediated through effects on various cell cycle proteins. Furthermore, rhBMP2 inhibited the growth of MDA-MB-231 cells injected both subcutaneously and intrafemorally.

Conclusion. In this model using human breast adenocarcinoma cell line, rhBMP2 has no stimulatory effect of tumor growth. Therefore, we can provide the basic science data to support the utilization in the management of patients with spine tumor in the future.

In this model using human breast adenocarcinoma cell line, recombinant human bone morphogenetic protein-2 has no stimulatory effect of tumor growth. Therefore, we can provide the basic science data to support the utilization in the management of patients with spine tumor in the future.

Departments of *Orthopaedic Surgery

Biochemistry

Pathology, and

§Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Republic of Korea

Department of Orthopaedic Surgery, University of California, Los Angeles, CA

Geriatric Research, Education, and Clinical Center, VA Greater Los Angeles, Health Care System, Sepulveda, CA

**Department of Medicine, University of California, Los Angeles, CA; and

††Biomedical Engineering Interdepartmental Program, University of California, Los Angeles, CA.

Address correspondence and reprint requests to Kwang-Bok Lee, MD, PhD, Department of Orthopaedic Surgery, Chonbuk National University Medical School, 567 Baekje-daero, Deokjin-gu, Jeonju, Jeonbuk 561-756, Republic of Korea; E-mail: osdr2815@naver.com

Acknowledgement date: August 2, 2012. Revision date: October 30, 2012. Acceptance date: November 2, 2012.

The device(s)/drug(s) that is/are the subject of this manuscript is/are not FDA-approved for this indication and is/are not commercially available in the United States.

Funds from the Biomedical Research Institute, Chonbuk National University Hospital, and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology funds (2011–0028928) were received to support this work.

Relevant financial activities outside the submitted work: board membership, patents, stocks, royalties.

© 2013 Lippincott Williams & Wilkins, Inc.