Soft matrix is a natural stimulator for cellular invasiveness

Zhizhan Gu, Fei Liu, Elina A. Tonkova, Soo Young Lee, Daniel J. Tschumperlin, Michael B. Brenner

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Directional mesenchymal cell invasion in vivo is understood to be a stimulated event and to be regulated by cytokines, chemokines, and types of extracellular matrix (ECM). Instead, by focusing on the cellular response to ECM stiffness, we found that soft ECM (low stiffness) itself is sufficient to prevent stable cell-to-cell adherens junction formation, up-regulate matrix metalloproteinase (MMP) secretion, promote MMP activity, and induce invadosome-like protrusion (ILP) formation. Consistently, similar ILP formation was also detected in a three-dimensional directional invasion assay in soft matrix. Primary human fibroblasts spontaneously form ILPs in a very narrow range of ECM stiffness (0.1-0.4 kPa), and such ILP formation is Src family kinase dependent. In contrast, spontaneous ILP formation in malignant cancer cells and fibrosarcoma cells occurs across a much wider range of ECM stiffness, and these tumor cell ILPs are also more prominent at lower stiffness. These findings suggest that ECM softness is a natural stimulator for cellular invasiveness.

Original languageEnglish (US)
Pages (from-to)457-469
Number of pages13
JournalMolecular biology of the cell
Volume25
Issue number4
DOIs
StatePublished - Feb 15 2014

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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