Elsevier

The Annals of Thoracic Surgery

Volume 80, Issue 3, September 2005, Pages 1028-1032
The Annals of Thoracic Surgery

Original article
General thoracic
Expression of Bone Morphogenetic Proteins in Human Lung Carcinomas

https://doi.org/10.1016/j.athoracsur.2005.03.094Get rights and content

Background

The bone morphogenetic proteins (BMP) are phytogenetically conserved proteins, which are essential for embryonic development. Bone morphogenetic protein-2 (BMP-2) was recently shown to be expressed in a small sample of lung carcinomas. Studies have suggested that BMP-2 may enhance tumor growth. The present study examined which BMP family members are expressed in non-small cell lung carcinomas (NSCLC). Furthermore, the frequency of BMP-2 overexpression and the types of lung carcinomas expressing BMP-2 were determined.

Methods

Tissue samples were obtained from the operating room and frozen in liquid nitrogen. Samples included metastatic NSCLC, benign lung tumors, adenocarcinoma, squamous cell carcinoma, bronchioloalveolar, and neuroendocrine carcinomas. Paired normal lung tissues served as the controls. The BMP-2, BMP-4, BMP-6, BMP-7, and growth differentiation factor 5 (GDF-5) expressions were examined by Western blot analysis.

Results

The BMP-4, BMP-6, BMP-7, and GDF-5 were infrequently expressed in NSCLC. The BMP-2 was expressed in 41 of 42 NSCLC with minimal expression in normal lung tissue; BMP-2 was expressed 17 fold higher than that of normal lung tissue. The BMP-2 was over-expressed in all subtypes of NSCLC, including neuroendocrine carcinomas. The BMP-2 expression was similar between squamous cell carcinomas and adenocarcinomas; however, bronchioloalveolar carcinomas tended to have a lower level of expression. The BMP-2 was not significantly expressed in benign lung tumors.

Conclusions

Bone morphogenetic protein-2 is the predominant family member expressed in NSCLC. The BMP-2 is overexpressed in the majority of human lung carcinomas independent of cell type.

Section snippets

Reagents

Primary antibodies mouse anti-BMP-2 (clone 65529), mouse anti-BMP-4 (clone 66119), mouse anti-BMP-6 (74219), mouse anti-BMP-7, and goat anti-growth differentiation factor 5 (anti-GDF-5) were purchased from R & D Systems (Minneapolis, MN). Recombinant proteins BMP-2, BMP-4, BMP-6, and GDF-5 were purchased from R & D Systems and were used as positive controls on Western blot analysis.

Tissue Specimens

Tissues were obtained directly from the operating room and immediately frozen in liquid nitrogen. All samples had

Expression of BMP Family Members in NSCLC

We found, by Western Blot analysis, high expression of the mature BMP-2 protein in the majority of NSCLC with little or no detectable expression in normal lung tissue (Fig 1). The BMP-2 was found to be expressed in all but one of the NSCLC examined (Table 1). The mature BMP-6 protein was detected in all the NSCLC examined, however it was expressed only slightly higher than that of normal lung tissue (Fig 1 and Table 1). Only low levels of expression of BMP-4 and GDF-5 were seen in a small

Comment

This paper demonstrates a high and frequent overexpression of BMP-2 in lung carcinomas. The mature active form of BMP-2 was aberrantly expressed in 98% of the NSCLC examined. BMP-2 is expressed in all types of lung carcinomas including both epithelial and neuroendocrine derived tumors. All of the adenocarcinomas and squamous cell carcinomas were found to overexpress BMP-2. The same level of BMP-2 expression was seen in both adenocarcinomas and squamous cell carcinomas. In this small analysis of

Acknowledgment

This study was funded by NIH Grant No. CA91919-01A1 and The Thoracic Surgery Foundation.

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