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(Chest. 2002;121:28S-29S.)
© 2002 American College of Chest Physicians

Partial Pneumonectomy Enhances Melanoma Metastasis to Mouse Lungs*

Lynn M. Brown, PhD; Danny R. Welch, PhD; D. Eugene Rannels, PhD and Stephen R. Rannels, PhD

* From the Penn State University College of Medicine, Hershey, PA.

Correspondence to: D. Eugene Rannels, PhD, Department of Cellular & Molecular Physiology, Penn State University College of Medicine, Hershey, PA 17033; e-mail: grannels{at}psu.edu

Tumor cell metastasis is the leading cause of morbidity and mortality associated with cancer. An improved understanding of the physiologic events that modulate metastases is needed to identify and employ effective treatments. Tissue growth can stimulate metastasis, markedly increasing both tumor incidence and multiplicity. In small mammals, left pneumonectomy (PNX) initiates rapid compensatory hyperplasia of the remnant lung lobes, which restores normal tissue mass, structure, and function. Our previous work1 demonstrated that PNX promotes pulmonary adenoma formation in carcinogen-treated mice. The present study tests the hypothesis that PNX enhances experimental metastasis to the lung. A left PNX or sham surgery was performed on syngeneic C57BL/6 mice at intervals prior to the IV injection of 5 x 104 B16F10 melanoma cells. Two weeks after injection, the animals were killed and the number of pulmonary melanoma metastases were enumerated. In control animals, the mean (± SEM) number of tumors ranged from 56 ± 8 to 105 ± 14. In mice that had been subjected to PNX 1 to 7 days prior to B16F10 cell injection, the mean tumor number ranged from 150 ± 22 to 235 ± 27, an increase of 77 to 260% over controls (p < 0.01). The largest difference was observed between day-5 groups, in which PNX mice had 3.6-fold more metastatic tumors than controls. Moreover, measurements of the tumor area revealed that PNX mice harbored a substantially larger lung tumor burden than did control animals. PNX had no effect on the growth of subcutaneous B16F10 melanoma tumors, suggesting that experimental melanoma metastasis was enhanced by local conditions associated with rapid lung growth. Because the lung is a frequent site for metastatic cancers, these results suggest that PNX is a relevant model in which to investigate the mechanisms that underlie the growth of metastases at a secondary site.


   Footnotes
 
Abbreviation: PNX = pneumonectomy

This research was supported by grants T32GM08619 and HL62869–02 from the National Institutes of Health.


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 References
 

  1. Brown, LM, Malkinson, AM, Rannels, DE, et al (1999) Compensatory lung growth after partial pneumonectomy enhances lung tumorigenesis induced by 3-methylcholanthrene. Cancer Res 59,5089-5092[Abstract/Free Full Text]



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