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Aktuelle Ernährungsmedizin 2001; 26(4): 116-120
DOI: 10.1055/s-2001-16657
HONORARY LECTURE
Honorary Lecture
© Georg Thieme Verlag Stuttgart · New York

Mechanisms of Tissue Catabolism and Reversal in Cancer[1]

Mechanismen des Gewebeabbaus bei Krebs und dessen BehebungM.  J. Tisdale
  • Pharmaceutical Sciences Research Institute, Aston University, Birmingham B4 7ET, United Kingdom
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Publication History

Publication Date:
27 August 2001 (online)

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Mechanismen des Gewebeabbaus bei Krebs und dessen Behebung

Die Kachexie bei Krebs betrifft nicht nur den Verlust von Fettgewebe, sondern auch den spezifischen Verlust von Skelettmuskulatur während viszerale Eiweißreserven verschont bleiben. Der Verlust von Fettgewebe kann entweder durch eine verminderte Syntheserate bei Hemmung der Lipoproteinlipase durch Zytokine oder durch eine vermehrte Lipolyserate durch lipolytische Substanzen aus dem Tumor verursacht sein. Aus dem Urin von kachektischen Patienten mit Krebs wurde ein fettmobilisierender Faktor (lipid mobilizing faktor, LMF) isoliert, der offensichtlich die Adenylatzyklase von Adipozyten stimuliert, entsprechend lipolytischen Hormonen, die zu einer Aktivierung der hormonsensitiven Lipase (HSL) führen. Es gibt jedoch keine Beweise für eine verminderte Lipoproteinlipase-Aktivität im Fettgewebe von Patienten mit Krebs, während ein Anstieg der hormonsensitiven Lipase beobachtet wird, was die Vermutung erlaubt, dass eine Steigerung des Fettabbaus von größerer Bedeutung für das Ausmaß der Fettmasse ist als ein Abfall der Synthese. Für den Verlust an Skelettmuskulatur wird angenommen, dass ein Anstieg im Eiweißabbau, verursacht durch den ATP-ubiquitinabhängigen Eiweißabbau, die Ursache ist. Ein die Proteolyse induzierender Faktor (proteolysis-inducing factor, PIF) wurde aus dem Urin von kachektischen Patienten mit unterschiedlichen Krebsformen isoliert, der direkt einen Muskeleiweißabbau induziert. Für die mehrfach ungesättigte Eicosapentaensäure (EPA) wurde gezeigt, dass sie den PIF-induzierten Eiweißabbau durch Hemmung der Bildung von 15-Hydroxyeicosatetraensäure (15-HETE) hemmt. In klinischen Studien an kachektischen Krebspatienten wurde gezeigt, dass EPA den Gewichtsverlust bremst und in Verbindung mit einer energiedichten Ernährung die fettfreie Körpermasse wieder ansteigen lässt. Diese Ergebnisse zeigen, dass neue Erkenntnisse zum Mechanismus des Verlustes von Körpersubstanz bei Krebs zu effektiven therapeutischen Strategien führen.

Summary

Cachexia in cancer involves not only loss of adipose tissue, but also specific loss of skeletal muscle, while visceral protein reserves are conserved. Loss of adipose tissue could arise either from a decreased synthetic rate, through cytokine inhibition of lipoprotein lipase (LPL), or through an increased lipolytic rate, due to tumour production of lipolytic substances. A lipid mobilizing factor (LMF) has been isolated from the urine of cachectic cancer patients and shown to stimulate adipocyte adenylate cyclase, as for lipolytic hormones, leading to activation of hormone sensitive lipase (HSL). However, there is no evidence for a decreased LPL in adipose tissue from cancer patients, while there is an increase in HSL, suggesting that an increase in lipid catabolism is more important than a decrease in synthesis in determining adipose mass. Loss of skeletal muscle is thought to arise from an increase in protein degradation mediated through the ATP-ubiquitin-dependent proteolytic pathway. A proteolysis-inducing factor (PIF) has been isolated from the urine of patients with cancer cachexia and a variety of tumour types and shown to induce muscle protein catabolism directly. The polyunsaturated fatty acid, eicosapentaenoic acid (EPA), has been found to be antagonistic to PIF-induced protein catabolism through inhibition of 15-hydroxyeicosatetraenoic acid (15-HETE) formation. In clinical trials with cachectic cancer patients EPA has been shown to stabilize the loss of body weight, and combined with an energy-dense nutritional supplement to increase lean body mass. These results show that knowledge of the mechanism of tissue wasting in cancer will lead to effective therapeutic strategies.

1 Honory Lecture bei der Tagung „Krebs und Ernährung” am 20. - 31. 3. 2001 in Berlin

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1 Honory Lecture bei der Tagung „Krebs und Ernährung” am 20. - 31. 3. 2001 in Berlin

Michael J. Tisdale,PhD, DSc 

Pharmaceutical Sciences Research Institute
Aston University

Birmingham B4 7ET
United Kingdom

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