Cancer Risk After Use of Recombinant Bone Morphogenetic Protein-2 for Spinal Arthrodesis

Carragee, Eugene J.; Chu, Gilbert; Rohatgi, Rajat; Hurwitz, Eric L.; Weiner, Bradley K.; Yoon, S. Tim; Comer, Garet C.; Kopjar, Branko

doi:10.2106/jbjs.l.01483

Cited by 234 publications

(155 citation statements)

References 24 publications

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“…BMP2 can promote cancer growth and metastases in gastric cancer (29), and carcinogen exposure induces BMP2 expression in the breast, resulting in stem cell transformation (30). Although controversial, use of the high dose recombinant BMP2 in patients has been linked with increased cancer rates (31)(32)(33). In contrast, loss of BMP signaling via BMP receptor mutations/deletion is associated with increased tumorigenesis and metastasis (34,35).…”

Section: Cd1333mentioning

confidence: 99%

Identifying an ovarian cancer cell hierarchy regulated by bone morphogenetic protein 2

Choi

Ingram

Yang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Whether human cancer follows a hierarchical or stochastic model of differentiation is controversial. Furthermore, the factors that regulate cancer stem-like cell (CSC) differentiation potential are largely unknown. We used a novel microfluidic single-cell culture method to directly observe the differentiation capacity of four heterogeneous ovarian cancer cell populations defined by the expression of the CSC markers aldehyde dehydrogenase (ALDH) and CD133. We evaluated 3,692 progeny from 2,833 cells. CD133+ cell expansion while suppressing the proliferation of ALDH − CD133 − cells. As such, BMP2 suppressed bulk cancer cell growth in vitro but increased tumor initiation rates, tumor growth, and chemotherapy resistance in vivo whereas BMP2 knockdown reduced CSC numbers, in vivo growth, and chemoresistance. These data suggest a hierarchical differentiation pattern in which BMP2 acts as a feedback mechanism promoting ovarian CSC expansion and suppressing progenitor proliferation. These results explain why BMP2 suppresses growth in vitro and promotes growth in vivo. Together, our results support BMP2 as a therapeutic target in ovarian cancer.ovarian cancer | cancer stem cells | BMP2 | differentiation capacity | hierarchical

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Section: Cd1333mentioning

confidence: 99%

Identifying an ovarian cancer cell hierarchy regulated by bone morphogenetic protein 2

Choi

Ingram

Yang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…86 Data from a multicenter, RCT of patients undergoing posterolateral fusions with BMP-2 did show a higher incidence of carcinoma among patients with BMP-2 treatment than those with autograft control. 87 Of note, multiple investigators have studied the link between BMP-2 and the incidence of cancer in large-scale studies and have not been able to replicate these findings. [88][89][90][91] Of note, most studies are limited by long-term follow-up.…”

Section: Risk Of Tumor Formation With Bmp-2mentioning

confidence: 99%

A Review of the Clinical Side Effects of Bone Morphogenetic Protein-2

James

LaChaud

Shen

et al. 2016

Tissue Engineering Part B: Reviews

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769

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Bone morphogenetic protein-2 (BMP-2) is currently the only Food and Drug Administration (FDA)-approved osteoinductive growth factor used as a bone graft substitute. However, with increasing clinical use of BMP-2, a growing and well-documented side effect profile has emerged. This includes postoperative inflammation and associated adverse effects, ectopic bone formation, osteoclast-mediated bone resorption, and inappropriate adipogenesis. Several large-scale studies have confirmed the relative frequency of adverse events associated with the clinical use of BMP-2, including life-threatening cervical spine swelling. In fact, the FDA has issued a warning of the potential life-threatening complications of BMP-2. This review summarizes the known adverse effects of BMP-2, including controversial areas such as tumorigenesis. Next, select animal models that replicate BMP-2's adverse clinical effects are discussed. Finally, potential molecules to mitigate the adverse effects of BMP-2 are reviewed. In summary, BMP-2 is a potent osteoinductive cytokine that has indeed revolutionized the bone graft substitute market; however, it simultaneously has accrued a worrisome side effect profile. Better understanding of these adverse effects among both translational scientists and clinicians will help determine the most appropriate and safe use of BMP-2 in the clinical setting.

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“…Pancreatic cancer was the only neoplasm that had a higher incidence in patients exposed to BMP. A recent study found a significant increase in cancer events after BMP exposure 7 . Of note, nine of the twenty cancer events in the BMP group were basal cell carcinoma or squamous cell carcinoma, which are non-SEER cancer types and frequently affect multiple sites.…”

mentioning

confidence: 96%

Cancer Risk from Bone Morphogenetic Protein Exposure in Spinal Arthrodesis

Kelly

Savage

Bentzen

et al. 2014

The Journal of Bone and Joint Surgery

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Cancer Risk After Use of Recombinant Bone Morphogenetic Protein-2 for Spinal Arthrodesis

Abstract: A high dose of 40 mg of rhBMP-2/CRM in lumbar spinal arthrodesis was associated with an increased risk of new cancer.

Cited by 234 publications

References 24 publications

Identifying an ovarian cancer cell hierarchy regulated by bone morphogenetic protein 2

Identifying an ovarian cancer cell hierarchy regulated by bone morphogenetic protein 2

A Review of the Clinical Side Effects of Bone Morphogenetic Protein-2

Cancer Risk from Bone Morphogenetic Protein Exposure in Spinal Arthrodesis

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