Mesenchymal Stem Cell-Induced DDR2 Mediates Stromal-Breast Cancer Interactions and Metastasis Growth
| Autor: | Kevin S. Tanager, Arjun Lama, Emily E. Martin, Natasha Medhora, Caroline Arellano-Garcia, Euisik Yoon, Maria E. Gonzalez, Yu Chih Chen, Kelley M. Kidwell, Celina G. Kleer, Talha Anwar, Chunxi Ge, Renny T. Franceschi |
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| Rok vydání: | 2017 |
| Předmět: |
collagen
0301 basic medicine Receptors Collagen Stromal cell Cell Breast Neoplasms Biology discoidin domain receptor Article General Biochemistry Genetics and Molecular Biology Metastasis Mice 03 medical and health sciences Discoidin Domain Receptor 2 breast cancer Downregulation and upregulation Cell Movement Cell Line Tumor medicine Animals Humans metastasis DDR2 EZH2 Neoplasm Metastasis Phosphorylation lcsh:QH301-705.5 mesenchymal stem cell Cell Proliferation Mesenchymal stem cell tumor stroma Cancer Mesenchymal Stem Cells Fibroblasts medicine.disease microenvironment 3. Good health Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) MCF-7 Cells Cancer research Female phosphorylated DDR2 Discoidin domain Signal Transduction |
| Zdroj: | Cell Reports, Vol 18, Iss 5, Pp 1215-1228 (2017) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2016.12.079 |
| Popis: | Increased collagen deposition by breast cancer (BC)-associated mesenchymal stem/multipotent stromal cells (MSC) promotes metastasis, but the mechanisms are unknown. Here, we report that the collagen receptor discoidin domain receptor 2 (DDR2) is essential for stromal-BC communication. In human BC metastasis, DDR2 is concordantly upregulated in metastatic cancer and multipotent mesenchymal stromal cells. In MSCs isolated from human BC metastasis, DDR2 maintains a fibroblastic phenotype with collagen deposition and induces pathological activation of DDR2 signaling in BC cells. Loss of DDR2 in MSCs impairs their ability to promote DDR2 phosphorylation in BC cells, as well as BC cell alignment, migration, and metastasis. Female ddr2-deficient mice homozygous for the slie mutation show inefficient spontaneous BC metastasis. These results point to a role for mesenchymal stem cell DDR2 in metastasis and suggest a therapeutic approach for metastatic BC. |
| Databáze: | OpenAIRE |
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