Bone morphogenetic protein-2/4 and bone morphogenetic protein receptor type IA expression in metastatic and nonmetastatic oral squamous cell carcinoma

Soares, Andrea Ferreira; Xavier, Ruth Lopes de Freitas; Miguel, Márcia Cristina da Costa; Souza, Lélia Batista de; Pinto, Leão Pereira

doi:10.1016/j.amjoto.2009.03.002

Cited by 14 publications

(14 citation statements)

References 28 publications

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“…Furthermore, the in vitro effects on expression profiles of protein kinases and the in vivo effects on animal survival after transient exposure of OSCCA cell lines to rhBMP‐2 suggest that this pathway is functional and capable of being activated. Our data also confirmed the findings from other studies that the BMP‐2 expression levels of normal oral mucosal cells are absent to weak 10, 21…”

Section: Discussionsupporting

confidence: 92%

rhBMP‐2 has adverse effects on human oral carcinoma cell lines in vivo

Kokorina

Lewis

Zakharkin³

et al. 2011

The Laryngoscope

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Objectives/Hypothesis To establish the relevance of the bone morphogenetic protein (BMP) signaling pathway in human oral squamous cell carcinoma (OSCCA) cell lines and determine if there is a biologic impact of stimulating this pathway with recombinant human (rh) BMP-2. Study Design In vitro laboratory investigations and in vivo analysis using an orthotopic animal model for oral cancer. Methods Gene expression profiles for BMP-2 and components of the BMP-signaling pathway were determined using reverse transcriptase-polymerase chain reaction. In vivo effects were evaluated using Kaplan-Meier survival analysis and studying histopathologic changes in established tumor xenografts with or without rhBMP-2 pretreatment. A phosphokinase array was used to detect levels of activation in signaling kinases. Results The BMP-2 gene was expressed in 90% of the 30 OSCCA cell lines tested. Gene expression of all components of the BMP-signaling pathway was highly conserved. Tumor xenografts established with rhBMP-2-treated cells showed more rapid local growth that resulted in worse animal survival as compared to the control group. These tumors had a more poorly differentiated morphology. Changes in protein kinases suggested interactions of BMP-2 signaling with the Wnt-β-catenin, and Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways. Conclusions Human OSCCA cell lines frequently express BMP-2 and all necessary components of the BMP-signaling pathway. Exogenous treatment of human OSCCA cell lines with rhBMP-2 prior to engraftment in an orthotopic animal model caused the subsequent tumors to be more locally aggressive with worse survival. Continued caution should be used for considering rhBMP-2 for reconstruction of bone defects in oral cancer patients.

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Section: Discussionsupporting

confidence: 92%

rhBMP‐2 has adverse effects on human oral carcinoma cell lines in vivo

Kokorina

Lewis

Zakharkin³

et al. 2011

The Laryngoscope

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“…In contrast to the findings of the present study, Soares et al. (12) observed weak immunoexpression of BMPR‐IA in metastatic OSCC. This difference might be explained by the fact that these authors studied carcinomas involving different oral sites.…”

Section: Discussioncontrasting

confidence: 99%

“…In the present study, regarding the percentage of BMP-2-positive cells, a predominance of score 3 and strong staining were observed in the metastatic and nonmetastatic groups. Immunohistochemical studies have shown a high expression of BMP-2 ⁄ 4 (12,20) and BMP-5 (20) in OSCC, whereas low levels of these proteins were observed in normal differentiated tissues and benign neoplasms of the mouth. However, in the present study, despite the strong immunoexpression of BMP-2 in non-metastatic lesions, the expression of BMPR-IA and BMPR-II was found to be low in this group.…”

Section: Discussionmentioning

confidence: 99%

“…Although various studies have suggested an important role of BMPs and their receptors in the development and progression of malignant tumors (12,13), there are no studies investigating the expression of BMPs and their receptors in LLSCC. Therefore, the objective of this study was to analyze the expression of BMP-2, BMP type IA receptor (BMPR-IA), and BMP type II receptor (BMPR-II) in metastatic and nonmetastatic LLSCCs and to determine the association with clinical stage and histologic grade of malignancy of the tumor.…”

Section: Introductionmentioning

confidence: 99%

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Immunoexpression of bone morphogenetic protein-2 (BMP-2), BMP receptor type IA, and BMP receptor type II in metastatic and non-metastatic lower lip squamous cell carcinoma

Carvalho

Nonaka

Araújo

et al. 2010

Journal of Oral Pathology &Amp; Medicine

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“…Compared with normal mucosa, human oral squamous cell carcinoma (SCC) tumours overexpress BMP2 , BMP4, BMP5 and BMPR1A (ALK3), and metastatic lymph nodes retain strong BMP2, BMP4 and BMP5 expression [130,131]. A recent tissue microarray of HNSCC found that the majority of samples [132] (98%) expressed BMP2 .…”

Section: Role Of Bmp Signalling In Cancer Pathogenesismentioning

confidence: 99%

Emerging roles of the bone morphogenetic protein pathway in cancer: potential therapeutic target for kinase inhibition

Jiramongkolchai

Owens

Hong

2016

Biochemical Society Transactions

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Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-β (TGF-β) family signalling pathway. Similar to TGF-β, the complex roles of BMPs in development and disease are demonstrated by their dichotomous roles in various cancers and cancer stages. Although early studies implicated BMP signalling in tumour suppressive phenotypes, the results of more recent experiments recognize BMPs as potent tumour promoters. Many of these complexities are becoming illuminated by understanding the role of BMPs in their contextual role in unique cell types of cancer and the impact of their surrounding tumour microenvironment. Here we review the emerging roles of BMP signalling in cancer, with a focus on the molecular underpinnings of BMP signalling in individual cancers as a valid therapeutic target for cancer prevention and treatment.

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Bone morphogenetic protein-2/4 and bone morphogenetic protein receptor type IA expression in metastatic and nonmetastatic oral squamous cell carcinoma

Cited by 14 publications

References 28 publications

rhBMP‐2 has adverse effects on human oral carcinoma cell lines in vivo

rhBMP‐2 has adverse effects on human oral carcinoma cell lines in vivo

Immunoexpression of bone morphogenetic protein-2 (BMP-2), BMP receptor type IA, and BMP receptor type II in metastatic and non-metastatic lower lip squamous cell carcinoma

Emerging roles of the bone morphogenetic protein pathway in cancer: potential therapeutic target for kinase inhibition

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