Mesenchymal Stem Cell-Induced DDR2 Mediates Stromal-Breast Cancer Interactions and Metastasis Growth

Maria E. Gonzalez, Emily E. Martin, Talha Anwar, Caroline Arellano-Garcia, Natasha Medhora, Arjun Lama, Yu Chih Chen, Kevin S. Tanager, Euisik Yoon, Kelley M. Kidwell, Chunxi Ge, Renny T. Franceschi, Celina G. Kleer

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1215-1228
Number of pages14
JournalCell Reports
Volume18
Issue number5
DOIs
Publication statusPublished - 2017 Jan 31

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Stem cells
Mesenchymal Stromal Cells
Collagen
Breast Neoplasms
Neoplasm Metastasis
Phosphorylation
Growth
Chemical activation
Communication
Discoidin Domain Receptor 2
Aptitude
Cell Movement
Phenotype
Mutation

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Gonzalez, M. E., Martin, E. E., Anwar, T., Arellano-Garcia, C., Medhora, N., Lama, A., ... Kleer, C. G. (2017). Mesenchymal Stem Cell-Induced DDR2 Mediates Stromal-Breast Cancer Interactions and Metastasis Growth. Cell Reports, 18(5), 1215-1228. https://doi.org/10.1016/j.celrep.2016.12.079
Gonzalez, Maria E. ; Martin, Emily E. ; Anwar, Talha ; Arellano-Garcia, Caroline ; Medhora, Natasha ; Lama, Arjun ; Chen, Yu Chih ; Tanager, Kevin S. ; Yoon, Euisik ; Kidwell, Kelley M. ; Ge, Chunxi ; Franceschi, Renny T. ; Kleer, Celina G. / Mesenchymal Stem Cell-Induced DDR2 Mediates Stromal-Breast Cancer Interactions and Metastasis Growth. In: Cell Reports. 2017 ; Vol. 18, No. 5. pp. 1215-1228.
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Gonzalez, ME, Martin, EE, Anwar, T, Arellano-Garcia, C, Medhora, N, Lama, A, Chen, YC, Tanager, KS, Yoon, E, Kidwell, KM, Ge, C, Franceschi, RT & Kleer, CG 2017, 'Mesenchymal Stem Cell-Induced DDR2 Mediates Stromal-Breast Cancer Interactions and Metastasis Growth', Cell Reports, vol. 18, no. 5, pp. 1215-1228. https://doi.org/10.1016/j.celrep.2016.12.079

Mesenchymal Stem Cell-Induced DDR2 Mediates Stromal-Breast Cancer Interactions and Metastasis Growth. / Gonzalez, Maria E.; Martin, Emily E.; Anwar, Talha; Arellano-Garcia, Caroline; Medhora, Natasha; Lama, Arjun; Chen, Yu Chih; Tanager, Kevin S.; Yoon, Euisik; Kidwell, Kelley M.; Ge, Chunxi; Franceschi, Renny T.; Kleer, Celina G.

In: Cell Reports, Vol. 18, No. 5, 31.01.2017, p. 1215-1228.

Research output: Contribution to journalArticle

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Gonzalez ME, Martin EE, Anwar T, Arellano-Garcia C, Medhora N, Lama A et al. Mesenchymal Stem Cell-Induced DDR2 Mediates Stromal-Breast Cancer Interactions and Metastasis Growth. Cell Reports. 2017 Jan 31;18(5):1215-1228. https://doi.org/10.1016/j.celrep.2016.12.079