Bone morphogenetic protein signaling in musculoskeletal cancer

Bami, Myrto; Mavrogenis, Andreas F.; Angelini, Andrea; Milonaki, Mandy; Mitsiokapa, Evanthia; Stamoulis, Dimitrios; Soucacos, Panayotis N.

doi:10.1007/s00432-016-2149-9

Cited by 20 publications

(11 citation statements)

References 109 publications

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“…While our study suggest a suppressive role for BMP2 in CRC, the precise role for the BMP signalling in tumour development is controversial since it has been reported to either promote or inhibit tumorogenesis [ 7 ]. Therefore it is possible that the effect of BMP signalling is dependent on tumour type as well as the status of other pathways in different cancers.…”

Section: Discussionmentioning

confidence: 81%

“…A number of studies have examined the association of abnormal BMP signalling with cancer initiation and/or progression. Changes in BMP signaling via the Smad cascade has been associated with a number of tumour types [ 6 , 7 ]. Also, BMP-2, -4 and -7 have exhibited altered expression in many types of malignancies including breast, prostate, osteosarcoma, glioma, ovarian, pancreatic, lung, and other cancers.…”

Section: Introductionmentioning

confidence: 99%

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Bone morphogenetic protein 2 (BMP2) induces growth suppression and enhances chemosensitivity of human colon cancer cells

et al. 2016

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BackgroundMolecular profiling of colorectal cancer (CRC) based on global gene expression has revealed multiple dysregulated signalling pathways associated with drug resistance and poor prognosis. However, the role of BMP2 signaling in CRC is not fully characterised.MethodsBioinformatics data analysis were conducted on the GSE21510 dataset. Leniviral technology was utilized to stably express BMP2 in the HCT116 CRC model. Gene expression profiling was conducted using Agilent microarray platform while data normalization and bioinformatics were conducted using GeneSpring software. Changes in gene expression were assessed using qRT-PCR. AlamarBlue assay was used to assess cell viability in vitro. In vivo experiments were conducted using SCID mice.ResultsOur data revealed frequent downregulation of BMP2 in primary CRC tissues. Additionally, interrogation of publically available gene expression datasets revealed significant downregulation of BMP2 in metastatic recurrent compared to non-metastatic cancer (p = 0.02). Global gene expression analysis in CRC cells over-expressing BMP2 revealed multiple dysregulated pathways mostly affecting cell cycle and DNA damage response. Concordantly, lentiviral-mediated re-expression of BMP2 inhibited HCT116 CRC growth, sphere formation, clonogenic potential, cell migration, and sensitized CRC cells to 5-fluorouracil (5-FU) in vitro. Additionally, BMP2 inhibited CRC tumor formation in SCID mice.ConclusionsOur data revealed an inhibitory role for BMP2 in CRC, suggesting that restoration of BMP2 expression could be a potential therapeutic strategy for CRC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-016-0355-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Bone morphogenetic protein 2 (BMP2) induces growth suppression and enhances chemosensitivity of human colon cancer cells

et al. 2016

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“…The malignant degree of osteosarcoma is extremely high. The prognosis is poor, and pulmonary metastasis can occur within several months, with the survival rate being only approximately 60% following amputation (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

miR-27a-3p promotes the malignant phenotypes of osteosarcoma by targeting ten-eleven translocation 1

Liu

et al. 2018

Int J Oncol

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Osteosarcoma has become one of the most common primary malignant tumors affecting children and adolescents. Although increasing evidence has indicated that microRNAs (miRNAs or miRs) play important roles in the development of osteosarcoma, the expression of miR‑27a‑3p and its effects on osteosarcoma are not yet fully understood. In the present study, our data demonstrated that the expression of miR‑27a‑3p in osteosarcoma cell lines was significantly higher than that in the normal human osteoblastic cell line, hFOB 1.19 cell (P<0.01). In order to explore the role of miR‑27a‑3p in the development and progression of osteosarcoma, the expression of miR‑27a‑3p was inhibited by transfection of the MG-63 cells with miR‑27a‑3p inhibitor. The results revealed that the cell proliferative ability significantly decreased (P<0.01), the number of apoptotic cells significantly increased (P<0.01) and the number of cells passing through the Transwell membrane was significantly reduced in the group transfected with the miR‑27a‑3p inhibitor (P<0.01). At the same time, the expression of E-cadherin and α-catenin was significantly upregulated (P<0.01), while the expression of vimentin was significantly downregulated in the group transfected with the miR‑27a‑3p inhibitor (P<0.01). Our results also revealed that the mRNA expression of ten-eleven translocation 1 (TET1) in the osteosarcoma cells was significantly downregulated compared with that in the hFOB 1.19 cells (P<0.01). Luciferase reporter system analysis indicated that miR‑27a‑3p recognized the TET1 3'-UTR. The protein expression of TET1 significantly increased in the group transfected with the miR‑27a‑3p inhibitor. The results from CCK-8 assay, flow cytometric assay and Transwell invasion analysis revealed that TET1 knockdown inhibited the biological effects induced by the downregulation of miR‑27a‑3p. Taken together, the findings of this study indicate that miR‑27a‑3p is upregulated, while TET1 is downregulated in human osteosarcoma cells. miR‑27a‑3p inhibition suppresses the proliferation and invasion of osteosarcoma cells, and promotes cell apoptosis via the negative regulation of TET1. miR‑27a‑3p/TET1 may thus be a potential target for the treatment of osteosarcoma.

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“…An autograft could have been considered for the same purpose. However, the use of a cancellous autograft to promote the healing of the arthrodesis is somewhat controversial because there is some evidence that bone morphogenic protein, which is present in cancellous allograft, may actually promote tumorigenesis in osteosarcoma in vitro . This has not been evaluated in canine osteosarcoma models.…”

Section: Discussionmentioning

confidence: 99%

“…However, the use of a cancellous autograft to promote the healing of the arthrodesis is somewhat controversial because there is some evidence that bone morphogenic protein, which is present in cancellous allograft, 17 may actually promote tumorigenesis in osteosarcoma in vitro. [18][19][20] This has not been evaluated in canine osteosarcoma models. There are 2 specific considerations of this technique that the authors consider worth further discussion.…”

Section: Discussionmentioning

confidence: 99%

Limb shortening as a strategy for limb sparing treatment of appendicular osteosarcoma of the distal radius in a dog

Boston

Skinner

2017

Veterinary Surgery

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Objective: To develop and report a novel limb sparing technique for the distal radius in a dog. Study design: Case report.Animal: A 14-year-old, female spayed Labrador Retriever with an osteosarcoma of the right distal radius and a pathological fracture. A previous mast cell tumor had been treated 5 years prior to presentation with marginal excision and a full-course radiation over the right metacarpal bones. The dog had received 2 doses of palliative radiation just prior to presentation.Methods: A standard resection of the distal radius was used as a strategy to salvage the limb. Instead of replacing the 6-cm bone defect with an endoprosthesis, the limb was acutely shortened and a carpal arthrodesis plate was applied.Results: Postoperative function was good and limb shortening was well-tolerated. Radiographic evidence of early bone healing was noted at the osteotomy site. The dog experienced 3 postoperative complications: a focal area of skin necrosis managed successfully via surgical revision; infection resolving after long-term antibiotherapy; and a fracture of the third metacarpal bone through a screw hole, managed via screw removal and a custom external prosthesis. The patient was euthanatized due to presumptive chemotherapy complications 127 days after the procedure. Conclusion:Limb shortening limb salvage is technically feasible and can result in excellent limb use postoperatively, in spite of a significant loss in limb length.

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Bone morphogenetic protein signaling in musculoskeletal cancer

Abstract: The review emphasizes on the role of BMP signaling in the initiation and progression of musculoskeletal cancer.

Cited by 20 publications

References 109 publications

Bone morphogenetic protein 2 (BMP2) induces growth suppression and enhances chemosensitivity of human colon cancer cells

Bone morphogenetic protein 2 (BMP2) induces growth suppression and enhances chemosensitivity of human colon cancer cells

miR-27a-3p promotes the malignant phenotypes of osteosarcoma by targeting ten-eleven translocation 1

Limb shortening as a strategy for limb sparing treatment of appendicular osteosarcoma of the distal radius in a dog

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