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Histochemistry and Cell Biology

, Volume 138, Issue 5, pp 803–813 | Cite as

Cancer cachexia alters intracellular surfactant metabolism but not total alveolar surface area

  • Tilman Graulich
  • Suman Kumar Das
  • Gabriela Krasteva
  • Clemens Ruppert
  • Lars Wessels
  • Gerald Hoefler
  • Christian MühlfeldEmail author
Original Paper

Abstract

Dyspnoea is frequently observed in cancer cachectic patients. Little is known whether this is accompanied by structural or functional alterations of the lung. We hypothesized that in analogy to calorie restriction cancer cachexia leads to loss of alveolar surface area and surfactant. Mice were subjected to subcutaneous injection of Lewis lung carcinoma cells (tumour group, TG) or saline (control group, CG). Twenty-one days later blood samples and the lungs were taken. Using design-based stereology, the alveolar surface area and the lamellar body (Lb) content were quantified. Messenger RNA expression of surfactant proteins, ABCA3 and various growth factors was investigated by quantitative RT-PCR. Intraalveolar surfactant subtype composition was analyzed by differential centrifugation. TG mice showed reduced body weight and anaemia but no reduction of lung volume or alveolar surface area. The volume of Lb was significantly reduced and mRNA levels of ABCA3 transporter tended to be lower in TG versus CG. Surfactant protein expression and the ratio between active and inactive intraalveolar surfactant subtypes were not altered in TG. Growth factor mRNA levels were not different between CG and TG lungs but the tumour expressed growth factor mRNA. Vascular endothelial growth factor was significantly enhanced in blood plasma. The present study demonstrates structural alterations of the lung associated with cancer cachexia. These include reduction of Lb content despite normal intraalveolar surfactant and alveolar surface area. The pulmonary phenotype of the cancer cachectic mouse differs from the calorie restricted mouse possibly due to growth factors released from the tumour tissue.

Keywords

Cancer cachexia Stereology Electron microscopy Alveolar remodelling Surfactant 

Notes

Acknowledgments

The authors are grateful to Petra Hartmann, Gerhard Kripp, Gerd Magdowski, Tamara Papadakis, and Silvia Schauer for expert technical assistance. The authors wish to thank the Verein zur Förderung der Krebsforschung in Gießen e. V. for a research grant (to CM). SKD was funded in part by the FWF grant F30 “Lipotoxicity” project P13 (to GH) and by the PhD program Molecular Medicine of the Medical University of Graz. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Tilman Graulich
    • 1
  • Suman Kumar Das
    • 2
  • Gabriela Krasteva
    • 1
    • 3
  • Clemens Ruppert
    • 3
    • 4
  • Lars Wessels
    • 1
  • Gerald Hoefler
    • 2
  • Christian Mühlfeld
    • 1
    • 5
    • 6
    Email author
  1. 1.Institute of Anatomy and Cell BiologyJustus-Liebig-University GiessenGiessenGermany
  2. 2.Institute of PathologyMedical University GrazGrazAustria
  3. 3.German Center for Lung Research, DZL-UGMLCGiessenGermany
  4. 4.Department of Internal MedicineJustus-Liebig-University GiessenGiessenGermany
  5. 5.Institute of Functional and Applied AnatomyHannover Medical SchoolHannoverGermany
  6. 6.German Center for Lung Research, DZL-BREATHHannoverGermany

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