Zusammenfassung
Tumoren des Magen-Darm-Traktes unter Einschluss von Malignomen des Magens, des Kolorektum,
der Leber und des Pankreas umfassen weltweit über 50 % aller Tumoren. Die 5-Jahres-Überlebensrate
schwankt zwischen über 50 % bei kolorektalen Tumoren und liegt unter 1 % beim Pankreaskarzinom,
wobei Überlebenszeit und Sterblichkeitsrate bei Tumoren des Magen-Darm-Traktes in
direkter Korrelation mit der Metastasierungskapazität stehen. Tetraspanine sind eine
relativ neue Familie von Membranproteinen, die vornehmlich über die Bildung von Komplexen
mit weiteren Tetraspaninen und einer Vielzahl weiterer Molekülfamilien agieren und
diese in definierten Membrandomänen zusammenführen. Diese lipidreichen Membrandomänen
sind in spezieller Weise zur Initiation von Signaltransduktionskaskaden geeignet.
Komplexbildung, die Generierung einer Plattform für Signaltransduktion und ihrer Eigenschaft
präferenziell in Vesikelform, sog. Exosomen, von der Tumorzelle freigesetzt zu werden,
prädestinieren Tetraspanine für eine zentrale Rolle bei allen Schritten der Metastasierungskaskade.
In Anbetracht dieser multiplen Involvierung der Tetraspanine in den Metastasierungsprozess
und eines sich in den letzten Jahren zunehmend experimentell festigenden Konzepts
zum Prozess der Metastasierung sind diesem kurzen Überblick über die Funktion von
Tetraspaninen, die aus heutiger Sicht zentralen Elemente der Tumorprogression, reversible
Differenzierung von Tumorstammzellen und Bedeutung der Tumor-Wirt-Beziehung, vorangestellt.
Abstract
Tumors of the gastrointestinal tract - gastric, colorectal, pancreatic and liver tumors
- account for over 50 % of cancer worldwide. The 5-year survival rate varies from
> 50 % in colorectal to < 1 % in pancreatic cancer. The high cancer death rate strikingly
correlates with the high metastasizing capacity of most gastrointestinal tumors. Therefore
and because during the last decade several important hypotheses on metastasis formation
could be settled on solid experimental ground, this review will first provide a brief
outline on the currently most accepted view of tumor progression and then discuss
whether and how the rather new family of tetraspanin molecules might contribute to
cancer progression. Notably, some members of this family, in particular, CD82/KAI1
are known as metastasis suppressor genes, while others like CD151 and CO-029 are supposed
to promote metastasis formation. The underlying mechanisms are beginning to become
unraveled. Tetraspanins assemble complexes of different tetraspanins, integrins and
additional transmembrane molecules in microdomains that serve as signaling platform.
By creating proximity, tetraspanins modulate functional activity of the associating
molecules. In addition, tetraspanins actively contribute to the intracellular traffic
of the associating molecules that includes vesicular budding and formation of exosomes
that are particularly rich in tetraspanins. Accordingly, the association of certain
tetraspanins with the metastatic phenotype as well as the definition of other tetraspanins
as metastasis suppressor genes has to be viewed from the perspective of molecular
complexes rather than the individual tetraspanin.
Schlüsselwörter
Tumorprogression - Angiogenese - Tetraspanine - CO-029 - CD82/KAI1
Key words
Tumor progression - angiogenesis - tetraspanins - CO-029 - CD82/KAI1
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Dr. Margot Zöller
Department of Tumor Progression and Tumor Defense, German Cancer Research Center
Im Neuenheimer Feld 280
69120 Heidelberg
Germany
Telefon: ++49/62 21/42 24 54
Fax: ++49/62 21/43 47 60
eMail: m.zoeller@dkfz.de
