Entstehung und Metastasierung des Pankreaskarzinoms mit Fokus auf Tumorhypoxie, EMT und Krebsstammzellen

Zusammenfassung

Entstehung, Wachstum und Metastasierung von malignen Tumoren erscheinen heute aufgrund jüngster wissenschaftlicher Erkenntnisse in einem neuen Licht. Die Krebsstammzell- (KSZ-)Theorie erklärt, warum Tumore wachsen, streuen und eine konventionelle Tumortherapie überleben. Am Beispiel des aggressiv und hoch invasiv wachsenden Bauchspeicheldrüsenkrebs gibt der vorliegende Artikel eine Übersicht über Mechanismen des Wachstums und der Metastasierung von malignen Tumoren. Dabei fokussiert der Artikel auf die Rolle der Tumorhypoxie bei der Entstehung von KSZ und der Epithelialen-Mesenchymalen Transition (EMT) bei der Metastasierung.

Summary

Due to new scientific findings, initiation, growth and metastasis of malignant tumors appear in new light today. The cancer stem cell (CSC) theory explains why tumors expand, invade and survive conventional tumor therapy. Using the example of aggressive and highly invasive pancreatic cancer the present article gives an overview about mechanisms of initiation and metastasis of this tumor entity. In the last years growing evidence underlines the importance of the tumor microenvironment as rout of tumor growth and metastasis. An important factor at this is tumor hypoxia, since an oxygen-depleted tumor region activates a signal transduction cascade, which favors tumor growth and metastasis. Under hypoxic growth conditions the presence of cancer stem cell markers is enhanced, which are thereafter induced to undergo epithelial-mesenchymal transition by oxygen-depletion. Several in vitro and animal examinations demonstrate that hypoxia creates the prerequisites for invasion of tumor cells to distant organs. Therapeutic aim of a new concept in therapy of pancreatic cancer does therefore not focus to elimination of cancer stem cells itself. Rather the rout of development of cancer stem cells should be targeted by elimination of tumor hypoxia.

Schlüsselwörter

Krebsstammzellen - Metastasierung - Epitheliale-Mesenchymale Transition - Tumorhypoxie - Pankreaskarzinom

Keywords

Cancer stem cells - metastasis - epithelial-mesenchymal transition - tumor hypoxia - pancreatic cancer

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