Abstract
Metastasis formation is the final result of a cascade of events that primary tumor cells pass through by changing their phenotype and the crosstalk with the tumor environment. Molecules involved in this process are besides others tetraspanins, which surprisingly can either inhibit or promote metastasis formation. These opposing activities are supposed to rely on the special feature of tetraspanins that mostly act via modulating the activity of a multitude of associating molecules. Tetraspanins assemble a web between themselves and other associating molecules in special glycolipid-enriched membrane microdomains, which function as signaling platform, but are also prone for internalization. Internalization of tetraspanins and associated molecules by itself can contribute to promotion or inhibition of tumor progression. Notably, the internalized tetraspanin web is abundantly recovered in exosomes, small vesicles that derive from internalized membrane microdomains. Thus, it appears reasonable to assume that exosomal tetraspanins are of major importance for the crosstalk between the metastasizing tumor cell, the tumor stroma, the vessel endothelium, and the premetastatic organ. I will briefly introduce the structure of tetraspanins and their presently known main functional activities as a starting point to appreciate the contribution of selective tetraspanins in metastasis promotion and inhibition.
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Acknowledgments
This work was supported by the Deutsche Forschungsgemeinschaft (grant ZO 40/12-1), the Deutsche Krebshilfe, and the Tumorzentrum Heidelberg/Mannheim.
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Zöller, M. (2010). Tetraspanins and Cancer Metastasis. In: Bagley, R. (eds) The Tumor Microenvironment. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6615-5_26
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