Stromal fibroblasts facilitate cancer cell invasion by a novel invadopodia-independent matrix degradation process
| Autor: | Li Qiang, Hong Cao, Robbin D Eppinga, Jing Chen, Gina L. Razidlo, Mark A. McNiven, Eugene W. Krueger |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Dynamins Cancer Research Stromal cell Podosome cancer associated fibroblasts Breast Neoplasms Matrix metalloproteinase Biology Article 03 medical and health sciences Dynamin II Genetics metastasis Humans Neoplasm Invasiveness Neoplasm Metastasis cdc42 GTP-Binding Protein Molecular Biology invadopodia Tumor microenvironment Mesenchymal stem cell Dynamin 2 matrix metalloproteinases Fibroblasts Xenograft Model Antitumor Assays Cell biology 030104 developmental biology src-Family Kinases Cdc42 GTP-Binding Protein Invadopodia Podosomes Proteolysis Cancer-Associated Fibroblasts Female Stromal Cells Carcinoma Pancreatic Ductal |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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