The mature bone morphogenetic protein-2 is aberrantly expressed in non-small cell lung carcinomas and stimulates tumor growth of A549 cells.

Abstract

To help identify genes, which may regulate metastasis in lung cancer, we performed representational difference analysis between a patient-derived non-small cell lung carcinoma (NSCLC) and immortalized normal human bronchial epithelial cells. This analysis revealed that bone morphogenetic proteins-2/4 (BMP) mRNA was expressed in the lung carcinoma. BMP-2/4 are known to induce pluripotent cell differentiation, enhance cell migration and stimulate proliferation during embryonic development. Despite being powerful morphogens it is not known whether BMP-2/4 have significant biological activity in human carcinomas. Furthermore, it has not been established whether the mature active BMP-2/4 protein is aberrantly expressed in patient-derived tumors. The purpose of this study was to determine whether the expression of the mature BMP-2/4 protein is disregulated in human lung carcinomas and to establish whether it has adverse biological activity. This study reveals that the mature BMP-2 protein, but not BMP-4, is highly over-expressed in human NCSLC with little to no expression in normal lung tissue or benign lung tumors. The expression of BMP-2 localized specifically to the cancer cells. Recombinant BMP-2 stimulated in vitro, the migration and invasiveness of the A549 and H7249 human lung cancer cell lines. In vivo, recombinant BMP-2 enhanced the growth of tumors formed from A549 cells injected subcutaneously into nude mice. Furthermore, inhibition of BMP-2 activity with either recombinant noggin or anti-BMP-2 antibody resulted in a significant reduction in tumor growth. This study shows that expression of the mature BMP-2 protein is disregulated in the majority of NSCLC. BMP-2 enhancement of tumor cell migration and invasion, as well as stimulating tumor growth in vivo, suggests it has important biological activity in lung carcinomas.

• Authors: Elaine M Langenfeld, Steve E Calvano, Fadi Abou-Nukta, Stephen F Lowry, Peter Amenta, John Langenfeld
• Journal: Carcinogenesis (Carcinogenesis) Vol. 24 Issue 9 Pg. 1445-54 (Sep 2003) ISSN: 0143-3334 [Print] England
• PMID: 12819188 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• BMP2 protein, human
• BMP4 protein, human
• Bmp2 protein, mouse
• Bmp4 protein, mouse
• Bone Morphogenetic Protein 2
• Bone Morphogenetic Protein 4
• Bone Morphogenetic Proteins
• Recombinant Proteins
• Transforming Growth Factor beta
• recombinant human bone morphogenetic protein-2

Topics

• Animals
• Bone Morphogenetic Protein 2
• Bone Morphogenetic Protein 4
• Bone Morphogenetic Proteins (genetics, metabolism, pharmacology)
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms (genetics, metabolism)
• Male
• Mice
• Neoplasm Invasiveness (pathology)
• Neoplasm Transplantation
• Recombinant Proteins (pharmacology)
• Transforming Growth Factor beta
• Tumor Cells, Cultured