Document Type
Article
Publication Date
3-3-2016
Department
Biology
Keywords
invadopodia, matrix metalloproteinases, Dynamin 2, metastasis, cancer associated fibroblasts
Abstract
Metastatic invasion of tumors into peripheral tissues is known to rely upon protease-mediated degradation of the surrounding stroma. This remodeling process utilizes complex, actin-based, specializations of the plasma membrane termed invadopodia that act both to sequester and release matrix metalloproteinases. Here we report that cells of mesenchymal origin, including tumor-associated fibroblasts, degrade substantial amounts of surrounding matrix by a mechanism independent of conventional invadopodia. These degradative sites lack the punctate shape of conventional invadopodia to spread along the cell base and are reticular and/or fibrous in character. In marked contrast to invadopodia, this degradation does not require the action of Src kinase, Cdc42, or Dyn2. Rather, inhibition of Dyn2 causes a dramatic upregulation of stromal matrix degradation. Further, expression and activity of matrix metalloproteinases are differentially regulated between tumor cells and stromal fibroblasts. This matrix remodeling by fibroblasts increases the invasive capacity of tumor cells, thereby illustrating how the tumor microenvironment can contribute to metastasis. These findings provide evidence for a novel matrix remodeling process conducted by stromal fibroblasts that is substantially more effective than conventional invadopodia, distinct in structural organization, and regulated by disparate molecular mechanisms.
Source Publication Title
Oncogene
Publisher
Nature Publishing Group
Volume
35
Issue
9
First Page
1099
DOI
10.1038/onc.2015.163
Recommended Citation
Cao, H., Eppinga, R., Razidio, G. L., Krueger, E. W., Chen, J., Qiang, L., & McNiven, M. A. (2016). Stromal Fibroblasts Facilitate Cancer Cell Invasion by a Novel Invadopodia-Independent Matrix Degradation Process. Oncogene, 35 (9), 1099. https://doi.org/10.1038/onc.2015.163
Comments
Copyright © 2016 by the Nature Publishing Group.