Abstract
PurposeBone 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.Experimental designThe 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.ResultsThere 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.ConclusionsIn the model systems tested, the addition of BMP-2 does not increase osteosarcoma proliferation, migration, invasion, or metastasis to the lungs.
Highlights
Osteosarcoma is a rare primary bone tumor, making up less than 1% of cancers in the United States.[1]
There was no significant difference in migration capacity, invasion, or cell proliferation between the Bone Morphogenetic Protein-2 (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
Summary
Osteosarcoma is a rare primary bone tumor, making up less than 1% of cancers in the United States.[1]. Extremity osteosarcomas were typically removed by performing amputations or disarticulations. [5] In the modern era, limb-salvage surgery offers patients an alternative to ablative procedures and is utilized in 90% of patients with extremity osteosarcomas. [6] These patients realize survival outcomes comparable to those who undergo amputations. Limb-salvage surgery is characterized by extirpation of the primary tumor and subsequent reconstruction, using either a structural allograft bone or an endoprosthesis. Allograft reconstruction is subject to several well-described complications including infection, allograft fracture, and non-union. Non-union at the allograft-host bone junction has been seen in over 25% of limb-salvage patients undergoing chemotherapy. [7] Patients who experience non-union frequently experience pain, delayed return to activities of daily living and additional surgery is required, leading to additional cost and burden for patients. Non-union at the allograft-host bone junction has been seen in over 25% of limb-salvage patients undergoing chemotherapy. [7] Patients who experience non-union frequently experience pain, delayed return to activities of daily living and additional surgery is required, leading to additional cost and burden for patients. [8]
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