ArticleCancer microenvironment : official journal of the International Cancer Microenvironment Society2016
Stiffened Extracellular Matrix and Signaling from Stromal Fibroblasts via Osteoprotegerin Regulate Tumor Cell Invasion in a 3-D Tumor in Situ Model.
Article in Cancer microenvironment : official journal of the International Cancer Microenvironment Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- 3DACS biomaterials science & engineering · 2023Pooled it
- A vascularized breast cancer spheroid platform for the ranked evaluation of tumor microenvironment-targeted drugs by light sheet fluorescence microscopy.Nature communications · 2024Article
- The first embryo, the origin of cancer and animal phylogeny. III. The totipotency as revealed by morphogenesis and the neoplasia controlled by cellular differentiation.Journal of biosciences · 2024Review
- The Extracellular Matrix: Its Composition, Function, Remodeling, and Role in Tumorigenesis.Biomimetics (Basel, Switzerland) · 2023Review
- Hyperelastic characterization reveals proteoglycans drive the nanoscale strain-stiffening response in hyaline cartilage.Journal of biomechanics · 2023Article
- ReshapingFrontiers in bioengineering and biotechnology · 2020Article
- Scaffold stiffness influences breast cancer cell invasion via EGFR-linked Mena upregulation and matrix remodeling.Matrix biology : journal of the International Society for Matrix Biology · 2020Article
- Mechanobiology of Cancer Stem Cells and Their Niche.Cancer microenvironment : official journal of the International Cancer Microenvironment Society · 2019Review
- The Role of Tumor Microenvironment in Chemoresistance: 3D Extracellular Matrices as Accomplices.International journal of molecular sciences · 2018Article
- Decoupling the effects of stiffness and fiber density on cellular behaviors via an interpenetrating network of gelatin-methacrylate and collagen.Biomaterials · 2017Article
- The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer.International journal of molecular sciences · 2017Review
- The β-catenin/YAP signaling axis is a key regulator of melanoma-associated fibroblasts.Signal transduction and targeted therapyArticle
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several changes have been described in the stroma surrounding a tumor, including changes in cellular composition, altered extracellular matrix composition and organization, and increases in stiffness. Tumor cells are influenced by the composition, organization, and mechanical properties of the microenvironment, and by signals from stromal cells. Here we sought to test whether signaling from stromal fibroblasts and/or the small change in stiffness observed in vivo surrounding epithelial tumors regulates tumor cell invasion from a model of a tumor in situ. We generated a novel tumor in situ model system in which a tumor spheroid is encased within a collagen-IV containing membrane and further encased within a collagen-I matrix of in vivo stiffness with or without fibroblasts. Effects of the matrix, fibroblasts or fibroblast signals were determined by observing the invasion of tumor cells into the matrix. Effects of reciprocal tumor cell signaling upon fibroblasts were determined by observing markers of fibroblast activation. We found that a stiffened matrix led to increased dissemination of MDA-MB-231 cells from tumor spheroids when no fibroblasts were present and that MCF10A cells maintained a more normal organization with a stiffened matrix. The presence of fibroblasts, or fibroblast conditioned media, attenuated the effect upon MDA-MB-231 cells. We also observed an attenuation of fibroblast activation associated gene expression in the presence of MDA-MB-231 cells, with a paradoxical increase in activation associated contractile activity. Furthermore, we identified osteoprotegerin as a soluble factor released by fibroblasts in the stiffened environment that is key to the inhibition of cell invasion.
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