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The success of anticancer therapies is often limited by heterogeneity within and between tumors. While much attention has been devoted to understanding the intrinsic molecular diversity of tumor cells, the surrounding tissue microenvironment is also highly complex and coevolves with tumor cells to drive clinical outcomes. Here, we propose that diverse types of solid tumors share common physical motifs that change in time and space, serving as universal regulators of malignancy. We use breast cancer and glioblastoma as instructive examples and highlight how invasion in both diseases is driven by the appropriation of structural guidance cues, contact-dependent heterotypic interactions with stromal cells, and elevated interstitial fluid pressure and flow. We discuss how engineering strategies show increasing value for measuring and modeling these physical propertiesfor mechanistic studies. Moreover, engineered systems offer great promise for developing and testing novel therapies that improve patient prognosis by normalizing the physical tumor microenvironment. [ABSTRACT FROM AUTHOR]

Obesity increases the risk and worsens the prognosis for breast cancer due, in part, to altered adipose stromal cell (ASC) behavior. Whether ASCs from obese individuals increase migration of breast cancer cells relative to their lean counterparts, however, remains unclear. To test this connection, multicellular spheroids composed of MCF10A‐derived tumor cell lines of varying malignant potential and lean or obese ASCs are embedded into collagen scaffolds mimicking the elastic moduli of interstitial breast adipose tissue. Confocal image analysis suggests that tumor cells alone migrate insignificantly under these conditions. However, direct cell‐cell contact with either lean or obese ASCs enables them to migrate collectively, whereby obese ASCs activate tumor cell migration more effectively than their lean counterparts. Time‐resolved optical coherence tomography imaging suggests that obese ASCs facilitate tumor cell migration by mediating contraction of local collagen fibers. Matrix metalloproteinase (MMP)‐dependent proteolytic activity significantly contributes to ASC‐mediated tumor cell invasion and collagen deformation. However, ASC contractility is also important, as co‐inhibition of both MMPs and contractility is necessary to completely abrogate ASC‐mediated tumor cell migration. These findings imply that obesity‐mediated changes of ASC phenotype may impact tumor cell migration and invasion with potential implications for breast cancer malignancy in obese patients. [ABSTRACT FROM AUTHOR]

Extracellular Matrix Remodelling: Obesity-Associated Adipose Stromal Cells Promote Breast Cancer Invasion through Direct Cell Contact and ECM Remodeling (Adv. Funct. Keywords: collagen; extracellular matrix remodeling; obesity; optical coherence tomography; tumor invasion EN collagen extracellular matrix remodeling obesity optical coherence tomography tumor invasion 1 1 1 11/27/20 20201125 NES 201125 In article number 1910650, Claudia Fischbach and co-workers combine collagen-embedded multicellular spheroids and advanced imaging to investigate the effect of adipose stromal cells (ASCs) on tumor cell invasion as a function of obesity. Obese ASCs increase collective tumor cell migration relative to lean ASCs by stimulating proteolytic and contractility-dependent collagen remode ling, providing insights into how obesity promotes breast cancer malignancy. [Extracted from the article]