New Wrinkle Between Cancer and Blood Coagulation: Metastasis and Cleavage of von Willebrand Factor by ADAM28
Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude met en évidence un mécanisme par lequel la métalloprotéase ADAM28, en clivant le facteur de von Willebrand, favorise le processus métastatique
Although metastasis accounts for the death of approximately 90% of patients with cancer (1), this field of research was of little interest to most scientists for most of the 20th century. The past decade, however, has witnessed an explosion of interest in metastasis, and the complexity of the process has become mind-boggling. New concepts describing the plethora of mechanisms involved in the metastatic process (eg, premetastatic niche formation, epithelial–mesenchymal transition [EMT], protease-independent cancer cell invasion) have forced us “to think outside the box” (1). In this issue of the Journal, Mochizuki et al. (2) provide novel experimental data explaining how aggressive types of cancer cells are able to avoid apoptosis in the circulatory system at metastatic sites. Prior studies by the authors had demonstrated that increased tumor tissue and serum levels of a metalloproteinase (a disintegrin and metalloproteinase [ADAM]28), whose functions are little known, correlated with poor prognosis and metastasis in patients with breast and lung cancer (3). The authors proposed that ADAM28 contributes to tumor growth by selective digestion of insulinlike growth factor binding protein 3 and connective tissue growth factor (3). However, the molecular mechanisms by which ADAM28 promotes experimental metastases remained elusive.
Using a yeast two-hybrid system to screen a human lung cDNA library to identify how ADAM28 promotes the progression of cancer, Mochizuki et al. (2) found that ADAM28 binds to and cleaves von Willebrand's factor (VWF). The surprising aspect of this report is the demonstration that physiological levels of VWF, a prominent plasma …
Journal of the National Cancer Institute , éditorial en libre accès, 2012