Organotypic breast tumor model elucidates dynamic remodeling of tumor microenvironment.

Organotypic breast tumor model elucidates dynamic remodeling of tumor microenvironment. Biomaterials. 2020 Apr;238:119853 Authors: Singh S, Ray LA, Shahi Thakuri P, Tran S, Konopka MC, Luker GD, Tavana H Abstract Fibroblasts are a critical component of tumor microenvironments and associate with cancer cells physically and biochemically during different stages of the disease. Existing cell culture models to study interactions between fibroblasts and cancer cells lack native tumor architecture or scalability. We developed a scalable organotypic model by robotically encapsulating a triple negative breast cancer (TNBC) cell spheroid within a natural extracellular matrix containing dispersed fibroblasts. We utilized an established CXCL12 - CXCR4 chemokine-receptor signaling in breast tumors to validate our model. Using imaging techniques and molecular analyses, we demonstrated that CXCL12-secreting fibroblasts have elevated activity of RhoA/ROCK/myosin light chain-2 pathway and rapidly and significantly contract collagen matrices. Signaling between TNBC cells and CXCL12-producing fibroblasts promoted matrix invasion of cancer cells by activating oncogenic mitogen-activated protein kinase signaling, whereas normal fibroblasts significantly diminished TNBC cell invasiveness. We demonstrated that disrupting CXCL12 - CXCR4 signaling using a molecular inhibitor significantly inhibited invasiveness of cancer cells, suggesting blocking of tumor-...
Source: Biomaterials - Category: Materials Science Authors: Tags: Biomaterials Source Type: research