Effects of Lewis lung carcinoma and B16 melanoma on the innervation of the mouse trachea.
Cancer patients often suffer from dyspnea the pathogenesis of which is incompletely understood. Both dyspnea and pulmonary diseases are closely linked to airway innervation. Recently, it was shown that Lewis lung carcinoma induces cardiac hypoinnervation in the mouse. We hypothesized that airway innervation undergoes similar changes as myocardial innervation and that this effect occurs in different mouse models of cancer. C57Bl6 mice were randomly assigned to subcutaneous injection of Lewis lung carcinoma cells (LLC, n=6), B16 melanoma cells (B16, n=6), or saline (control group, C, n=10). After 16 or 21 days, respectively, the trachea was processed for light and electron microscopic design-based stereology and the volume, surface area and length of axons ramifying in the tracheal wall were estimated. Body weight was reduced both in LLC and B16 vs. C. Hypoinnervation was present in both tumor groups compared to controls as volume and surface area of axons were significantly reduced in LLC and B16. However, the total length of tracheal axons and the mean number of axons per nerve fiber were reduced only in LLC but not in B16 compared to C indicating a differentially pronounced effect of cancer on tracheal innervation. In conclusion, reduced innervation of the trachea was observed in two different murine tumor models. These findings add to the pathophysiological concepts explaining cancer-related dyspnea and open new perspectives of treating this symptom.
Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, Aulweg 123, 35385 Giessen, Germany.
Tilman
T
Graulich
Institute of Pathology, Medical University Graz, Auenbruggerplatz 25, 8036 Graz, Austria.
Suman Kumar
SK
Das
Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, Aulweg 123, 35385 Giessen, Germany.
Lars
L
Wessels
Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, Aulweg 123, 35385 Giessen, Germany; University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
Wolfgang
W
Kummer
Institute of Pathology, Medical University Graz, Auenbruggerplatz 25, 8036 Graz, Austria.
Gerald
G
Hoefler
Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, Aulweg 123, 35385 Giessen, Germany; Institute of Functional and Applied Anatomy, Hannover Medical School, 30625 Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany. Electronic address: Muehlfeld.Christian@mh-hannover.de.
Christian
C
Mühlfeld
D000818:Animals; D001369:Axons / Q000473:pathology / Q000648:ultrastructure; D018827:Carcinoma, Lewis Lung / Q000473:pathology*; D048429:Cell Size; D005260:Female; D008546:Melanoma, Experimental / Q000473:pathology*; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009368:Neoplasm Transplantation; D011897:Random Allocation; D014132:Trachea / Q000294:innervation* / Q000648:ultrastructure
Airways; Autonomic nervous system; Cancer; Electron microscopy; Stereology