Rebuilding the microenvironment of primary tumors in humans: a focus on stroma.

Conventional tumor models have critical shortcomings in that they lack the complexity of the human stroma. The heterogeneous stroma is a central compartment of the tumor microenvironment (TME) that must be addressed in cancer research and precision medicine. To fully model the human tumor stroma, the deconstruction and reconstruction of tumor tissues have been suggested as new approaches for in vitro tumor modeling. In this review, we summarize the heterogeneity of tumor-associated stromal cells and general deconstruction approaches used to isolate patient-specific stromal cells from tumor tissue; we also address the effect of the deconstruction procedure on the characteristics of primary cells. Finally, perspectives on the future of reconstructed tumor models are discussed, with an emphasis on the essential prerequisites for developing authentic humanized tumor models.

Extracellular Matrix-Based Hydrogels to Tailoring Tumor Organoids.

When embedded into a three-dimensional (3D) matrix, cancer stem cells (or cancer-initiating cells) can grow into self-organizing organotypic structures called tumor organoids. During organoid formation, the matrix not only provides structural support but also delivers biochemical signals. Although increasing evidence indicates that the extracellular matrix (ECM) is an essential component of the tumor microenvironment during tumor development and progression, the influence of the ECM on organoid formation has been largely ignored; the ECM has only recently been recognized to play a role in the regulation of cancer cell phenotypes. We reviewed ECM-based hydrogels to tailoring tumor organoids and highlight the potential role of the ECM in the development of recapitulating malignant/invasive tumor organoids with enhanced capacity for in vitro representation of ECM-regulated tumor progression.