Tumor-associated Endo180 requires stromal-derived LOX to promote metastatic prostate cancer cell migration on human ECM surfaces

Caley, Matthew P.; King, Helen; Shah, Neel; Wang, Kai; Rodriguez-Teja, Mercedes; Gronau, Julian H.; Waxman, Jonathan; Sturge, Justin

Abstract

The diverse composition and structure of extracellular matrix (ECM) interfaces encountered by tumor cells at secondary tissue sites can influence metastatic progression. Extensive in vitro and in vivo data has confirmed that metastasizing tumor cells can adopt different migratory modes in response to their microenvironment. Here we present a model that uses human stromal cell-derived matrices to demonstrate that plasticity in tumor cell movement is controlled by the tumor-associated collagen receptor Endo180 (CD280, CLEC13E, KIAA0709, MRC2, TEM9, uPARAP) and the crosslinking of collagen fibers by stromal-derived lysyl oxidase (LOX). Human osteoblast-derived and fibroblast-derived ECM supported a rounded ‘amoeboid-like’ mode of cell migration and enhanced Endo180 expression in three prostate cancer cell lines (PC3, VCaP, DU145). Genetic silencing of Endo180 reverted PC3 cells from their rounded mode of migration towards a bipolar ‘mesenchymal-like’ mode of migration and blocked their translocation on human fibroblast-derived and osteoblast-derived matrices. The concomitant decrease in PC3 cell migration and increase in Endo180 expression induced by stromal LOX inhibition indicates that the Endo180-dependent rounded mode of prostate cancer cell migration requires ECM crosslinking. In conclusion, this study introduces a realistic in vitro model for the study of metastatic prostate cancer cell plasticity and pinpoints the cooperation between tumor-associated Endo180 and the stiff microenvironment imposed by stromal-derived LOX as a potential target for limiting metastatic progression in prostate cancer.

Citation

Caley, M. P., King, H., Shah, N., Wang, K., Rodriguez-Teja, M., Gronau, J. H., Waxman, J., & Sturge, J. (2016). Tumor-associated Endo180 requires stromal-derived LOX to promote metastatic prostate cancer cell migration on human ECM surfaces. Clinical & experimental metastasis, 33(2), 151-165. https://doi.org/10.1007/s10585-015-9765-7

• Journal Article Type: Article
• Acceptance Date: Nov 2, 2015
• Online Publication Date: Nov 13, 2015
• Publication Date: Feb 1, 2016
• Deposit Date: Jan 27, 2016
• Publicly Available Date: Nov 23, 2017
• Journal: Clinical and experimental metastasis
• Print ISSN: 0262-0898
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 33
• Issue: 2
• Pages: 151-165
• DOI: https://doi.org/10.1007/s10585-015-9765-7
• Keywords: Bone; Cell migration; Collagen; Fibroblast; Osteoblast; Prostate cancer
• Public URL: https://hull-repository.worktribe.com/output/384532
• Publisher URL: http://link.springer.com/article/10.1007%2Fs10585-015-9765-7
• Additional Information: This is a copy of an open access article published in Clinical and experimental metastasis, 2015. The published version of this article includes a link to supplementary material.
• Contract Date: Nov 23, 2017