3D bioprinting for reconstituting the cancer microenvironment.

The cancer microenvironment is known for its complexity, both in its content as well as its dynamic nature, which is difficult to study using two-dimensional (2D) cell culture models. Several advances in tissue engineering have allowed more physiologically relevant three-dimensional (3D) in vitro cancer models, such as spheroid cultures, biopolymer scaffolds, and cancer-on-a-chip devices. Although these models serve as powerful tools for dissecting the roles of various biochemical and biophysical cues in carcinoma initiation and progression, they lack the ability to control the organization of multiple cell types in a complex dynamic 3D architecture. By virtue of its ability to precisely define perfusable networks and position of various cell types in a high-throughput manner, 3D bioprinting has the potential to more closely recapitulate the cancer microenvironment, relative to current methods. In this review, we discuss the applications of 3D bioprinting in mimicking cancer microenvironment, their use in immunotherapy as prescreening tools, and overview of current bioprinted cancer models

Dynein‐Powered Cell Locomotion Guides Metastasis of Breast Cancer

Abstract The principal cause of death in cancer patients is metastasis, which remains an unresolved problem. Conventionally, metastatic dissemination is linked to actomyosin‐driven cell locomotion. However, the locomotion of cancer cells often does not strictly line up with the measured actomyosin forces. Here, a complementary mechanism of metastatic locomotion powered by dynein‐generated forces is identified. These forces arise within a non‐stretchable microtubule network and drive persistent contact guidance of migrating cancer cells along the biomimetic collagen fibers. It is also shown that the dynein‐powered locomotion becomes indispensable during invasive 3D migration within a tissue‐like luminal network formed by spatially confining granular hydrogel scaffolds (GHS) made up of microscale hydrogel particles (microgels). These results indicate that the complementary motricity mediated by dynein is always necessary and, in certain instances, sufficient for disseminating metastatic breast cancer cells. These findings advance the fundamental understanding of cell locomotion mechanisms and expand the spectrum of clinical targets against metastasis