Expression of Bone Morphogenetic Protein 7 in Lung Cancer and its Biological Impact on Lung Cancer Cells

Abstract

Background: Lung cancer is the leading cause of cancer-related death in the world, with metastasis being the main reason for the mortality. As a member of the bone morphogenetic protein (BMP) family, BMP7 has important biological functions in malignant tumours. As yet, however, there is little knowledge of the role of BMP7 and its cellular function in lung cancer. This study aimed to investigate the biological impact of BMP7 on lung cancer cells and the expression pattern of the molecule in clinical lung carcinomas. Materials and Methods: The expression pattern of BMP7 and its receptors was examined in different lung cancer cell lines and normal cells. The biological function of BMP7 in lung cancer cells was further evaluated. The impact of BMP7 on the downstream signalling, namely the activation of SMAD1 status, was assessed. BMP7 expression level was assessed in a cohort of human lung cancer samples (tumour, n=70; matched normal tissues, n=70), in association with patient clinical variables, using quantitative analysis of BMP7. Results: In vitro, it was found that recombinant human (rh)BMP7 significantly reduced cellular motility of lung cancer cell line, SK-MES1, and its adhesion to Matrigel (p<0.05). rhBMP7 was also able to significantly reduce invasion of lung cancer cells (p<0.05). We found that rhBMP7 had little effect on actual growth of the lung cells. In addition, BMP7 was able to regulate the phosphorylation of SMAD1, a downstream signalling intermediate of the BMP7 signalling pathway. The study further revealed that reduced levels of BMP7 in lung cancer tissues significantly correlated with lymph node metastasis for lung cancer patients (p<0.05). Conclusion: BMP7 protein is a pivotal regulator of cell motility in lung cancer with little impact on the growth of tumour cells. BMP7 expression is linked to lymph node involvement in patients with lung cancer. These results indicate that BMP7 plays a key role in regulating the progression of lung cancer.