*From the University of Colorado, Denver, CO; Memorial Sloan Kettering Cancer Center, New York, NY; and the National Cancer Institute, Rockville, MD.
Correspondence to: Robert J. Mason, MD, Associated Vice President, Academic Affairs, National Jewish Medical and Research Center, 1400 Jackson St, Denver, CO 80206; e-mail: firstname.lastname@example.org
Biomarkers for lung cancer would greatly improve our ability to detect, monitor, and treat patients with this deadly disease. Proteins secreted by pulmonary epithelial cells are excellent candidates for such biomarkers. We have previously reported1 that murine urethane-induced adenomas expressed surfactant proteins (SPs) including SP-D. To determine whether serum levels of SP-D would be a useful biomarker of parenchymal and airway diseases in mice, we developed an enzyme-linked immunosorbent assay using recombinant murine SP-D as the standard. The mean (± SD) serum levels of SP-D in normal mice were 5.0 ± 0.2 ng/mL (121 mice), in SP-D nulls were 0.04 ± 0.03 ng/mL (5 mice), and in SP-D transgenic mice were 63.6 ± 9.0 ng/mL (3 mice). In mice with urethane-induced adenomas, the mean levels were 50.8 ± 6.4 ng/mL (5 mice), and in mice with tumors regulated by an inducible mutated K-ras the levels were 158 ± 20 ng/mL (12 mice).
In another series of mice with genetically regulated tumors, the serum SP-D level correlated with tumor volume (40 mice; R2 = 0.84). Using a 99% confidence limit and a value of 11.4 ng/mL, the specificity was 100% and the sensitivity was 0.8. The level of SP-D in serum was verified by immunoblotting. By use of in situ hybridization, there was a neighborhood effect whereby type II cells near the tumor expressed more SP-D messenger RNA than did type II cells in the rest of the lung. The serum level of SP-D was also increased with lung inflammation after exposure to ozone or after ovalbumin challenge in sensitized BALB/c mice. Serum SP-D concentration is increased in mice bearing lung tumors and generally reflects the tumor burden, but is also elevated in mice with lung inflammation.
Abbreviation: SP = surfactant protein
This research was funded by Environmental Protection Agency grant R825702, and by National Institutes of Health grants HL-67671, CA 33497, and CA 96133.
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