Discoidin domain receptor 2 regulates the adhesion of fibroblasts to 3D collagen matrices

Kim,Daehwan; You,Eunae; Min,Na  Young; Lee,Kwang‑Ho; Kim,Hyoung  Kyu; Rhee,Sangmyung

doi:10.3892/ijmm.2013.1320

May 2013 Volume 31 Issue 5

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May 2013 Volume 31 Issue 5

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Article

Discoidin domain receptor 2 regulates the adhesion of fibroblasts to 3D collagen matrices

Authors:
- Daehwan Kim
- Eunae You
- Na Young Min
- Kwang‑Ho Lee
- Hyoung Kyu Kim
- Sangmyung Rhee
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Affiliations: Department of Life Science (BK21 Program), Chung-Ang University, Seoul 156-756, Republic of Korea, Department of Medicine and Microbiology, College of Medicine, Chungbuk National University, Cheungju 361-763, Republic of Korea
Pages: 1113-1118
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Published online on: March 27, 2013

https://doi.org/10.3892/ijmm.2013.1320
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Abstract

The collagen matrix constitutes the primary extracellular matrix (ECM) portion of mammalian connective tissues in which the interaction of the cell and the surrounding collagen fibers has a significant impact on cell and tissue physiology, including morphogenesis, development and motility. Discoidin domain receptors (DDR1 and DDR2) have been identified as the receptor tyrosine kinases that are activated upon collagen binding. However, there is a lack of evidence regarding the effect of DDRs on the mechanical interaction between fibroblasts and ECM. In this study, we demonstrated that one of the major phosphotyrosine proteins in human fibroblasts during 3D collagen matrix polymerization is DDR2. Treatment of fibroblasts in 3D collagen matrices with platelet-derived growth factor (PDFG) has been shown to increase DDR2 phosphorylation. Silencing of DDR2 with siRNA in fibroblasts significantly reduced the number of dendritic extensions regardless of whether cells were cultured in the collagen or fibronectin 3D matrices. Decreasing dendritic extensions in DDR2-silenced cells has also been shown to decrease the ability of fibroblast entanglement to collagen fibrils in 3D collagen matrices. Finally, we also showed that the silencing of DDR2 decreased the cell migration in 3D nested collagen matrices but had no effect on 3D floating matrix contraction. Collectively, these results suggest that DDR2 functioning is required for the membrane dynamics to control the mechanical attachment of fibroblasts to the 3D collagen matrices in an integrin-independent manner.

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1	Engler AJ, Sweeney HL, Discher DE and Schwarzbauer JE: Extracellular matrix elasticity directs stem cell differentiation. J Musculoskelet Neuronal Interact. 7:3352007.PubMed/NCBI
2	Friedl P and Bröcker EB: The biology of cell locomotion within three-dimensional extracellular matrix. Cell Mol Life Sci. 57:41–64. 2000. View Article : Google Scholar : PubMed/NCBI
3	Geiger B and Yamada KM: Molecular architecture and function of matrix adhesions. Cold Spring Harb Perspect Biol. 3:a0050332011. View Article : Google Scholar : PubMed/NCBI
4	Levental KR, Yu H, Kass L, et al: Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell. 139:891–906. 2009. View Article : Google Scholar : PubMed/NCBI
5	Castelló-Cros R and Cukierman E: Stromagenesis during tumorigenesis: characterization of tumor-associated fibroblasts and stroma-derived 3D matrices. Methods Mol Biol. 522:275–305. 2009.
6	Hynes RO: The extracellular matrix: not just pretty fibrils. Science. 326:1216–1219. 2009. View Article : Google Scholar : PubMed/NCBI
7	Larsen M, Artym VV, Green JA and Yamada KM: The matrix reorganized: extracellular matrix remodeling and integrin signaling. Curr Opin Cell Biol. 18:463–471. 2006. View Article : Google Scholar : PubMed/NCBI
8	Bershadsky AD, Ballestrem C, Carramusa L, et al: Assembly and mechanosensory function of focal adhesions: experiments and models. Eur J Cell Biol. 85:165–173. 2006. View Article : Google Scholar : PubMed/NCBI
9	Riveline D, Zamir E, Balaban NQ, et al: Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism. J Cell Biol. 153:1175–1186. 2001. View Article : Google Scholar
10	Grinnell F, Ho CH, Tamariz E, Lee DJ and Skuta G: Dendritic fibroblasts in three-dimensional collagen matrices. Mol Biol Cell. 14:384–395. 2003. View Article : Google Scholar : PubMed/NCBI
11	Jiang H and Grinnell F: Cell-matrix entanglement and mechanical anchorage of fibroblasts in three-dimensional collagen matrices. Mol Biol Cell. 16:5070–5076. 2005. View Article : Google Scholar : PubMed/NCBI
12	Vogel W, Gish GD, Alves F and Pawson T: The discoidin domain receptor tyrosine kinases are activated by collagen. Mol Cell. 1:13–23. 1997. View Article : Google Scholar : PubMed/NCBI
13	Vogel W: Discoidin domain receptors: structural relations and functional implications. FASEB J. 13(Suppl): S77–S82. 1999.PubMed/NCBI
14	Vogel WF, Abdulhussein R and Ford CE: Sensing extracellular matrix: an update on discoidin domain receptor function. Cell Signal. 18:1108–1116. 2006. View Article : Google Scholar : PubMed/NCBI
15	Huang Y, Arora P, McCulloch CA and Vogel WF: The collagen receptor DDR1 regulates cell spreading and motility by associating with myosin IIA. J Cell Sci. 122:1637–1646. 2009. View Article : Google Scholar : PubMed/NCBI
16	Rhee S and Grinnell F: P21-activated kinase 1: convergence point in PDGF- and LPA-stimulated collagen matrix contraction by human fibroblasts. J Cell Biol. 172:423–432. 2006. View Article : Google Scholar : PubMed/NCBI
17	Kim D, You E and Rhee S: Dynein regulates cell migration depending on substrate rigidity. Int J Mol Med. 29:440–446. 2012.PubMed/NCBI
18	Rhee S, Jiang H, Ho CH and Grinnell F: Microtubule function in fibroblast spreading is modulated according to the tension state of cell-matrix interactions. Proc Natl Acad Sci USA. 104:5425–5430. 2007. View Article : Google Scholar : PubMed/NCBI
19	Provenzano PP, Inman DR, Eliceiri KW, Trier SM and Keely PJ: Contact guidance mediated three-dimensional cell migration is regulated by Rho/ROCK-dependent matrix reorganization. Biophys J. 95:5374–5384. 2008. View Article : Google Scholar
20	Grinnell F, Rocha LB, Iucu C, Rhee S and Jiang H: Nested collagen matrices: a new model to study migration of human fibroblast populations in three dimensions. Exp Cell Res. 312:86–94. 2006.
21	Blissett AR, Garbellini D, Calomeni EP, Mihai C, Elton TS and Agarwal G: Regulation of collagen fibrillogenesis by cell-surface expression of kinase dead DDR2. J Mol Biol. 385:902–911. 2009. View Article : Google Scholar : PubMed/NCBI
22	Hachehouche LN, Chetoui N and Aoudjit F: Implication of discoidin domain receptor 1 in T cell migration in three-dimensional collagen. Mol Immunol. 47:1866–1869. 2010. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Discoidin domain receptor 2 regulates the adhesion of fibroblasts to 3D collagen matrices

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