Gill Jonathan, Connolly Patrick, Roth Michael, Chung So Hak, Zhang Wendong, Piperdi Sajida, Hoang Bang, Yang Rui, Guzik Hillary, Morris Jonathan, Gorlick Richard, Geller David S
Division of Pediatric Hematology/Oncology and Blood & Marrow Cell Transplantation, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx New York, United States of America.
Kosin University College of Medicine, Busan, Korea.
PLoS One. 2017 Mar 6;12(3):e0173322. doi: 10.1371/journal.pone.0173322. eCollection 2017.
Bone Morphogenetic Protein-2 (BMP-2) may offer the potential to enhance allograft-host osseous union in limb-salvage surgery following osteosarcoma resection. However, there is concern regarding the effect of locally applied BMP-2 on tumor recurrence and metastasis. The purpose of this project was to evaluate the effect of exogenous BMP-2 on osteosarcoma migration and invasion across a panel of tumor cell lines in vitro and to characterize the effect of BMP-2 on pulmonary osteosarcoma metastasis within a xenograft model.
The effect of BMP-2 on in vitro tumor growth and development was assessed across multiple standard and patient-derived xenograft osteosarcoma cell lines. Tumor migration capacity, invasion, and cell proliferation were characterized. In addition, the effect on metastasis was measured using a xenograft model following tail-vein injection. The effect of exogenous BMP-2 on the development of metastases was measured following both single and multiple BMP-2 administrations.
There was no significant difference in migration capacity, invasion, or cell proliferation between the BMP-2 treated and the untreated osteosarcoma cell lines. There was no significant difference in pulmonary metastases between either the single-dose or multi-dose BMP-2 treated animals and the untreated control animals.
In the model systems tested, the addition of BMP-2 does not increase osteosarcoma proliferation, migration, invasion, or metastasis to the lungs.
骨形态发生蛋白-2(BMP-2)可能具有增强骨肉瘤切除术后保肢手术中同种异体移植骨与宿主骨愈合的潜力。然而,人们担心局部应用BMP-2对肿瘤复发和转移的影响。本项目的目的是评估外源性BMP-2对一组骨肉瘤细胞系体外迁移和侵袭的影响,并在异种移植模型中表征BMP-2对肺骨肉瘤转移的影响。
在多个标准和患者来源的异种移植骨肉瘤细胞系中评估BMP-2对体外肿瘤生长和发育的影响。对肿瘤迁移能力、侵袭和细胞增殖进行表征。此外,在尾静脉注射后使用异种移植模型测量对转移的影响。在单次和多次给予BMP-2后测量外源性BMP-2对转移发展的影响。
BMP-2处理组和未处理组骨肉瘤细胞系之间在迁移能力、侵袭或细胞增殖方面没有显著差异。单剂量或多剂量BMP-2处理的动物与未处理的对照动物在肺转移方面没有显著差异。
在所测试的模型系统中,添加BMP-2不会增加骨肉瘤的增殖、迁移、侵袭或肺转移。