Collective Polarization of Cancer Cells at the Monolayer Boundary

Abstract

Cell polarization, a process depending on both intracellular and intercellular interactions, is crucial for collective cell migration that commonly emerges in embryonic development, tissue morphogenesis, wound healing and cancer metastasis. Although invasive cancer cells display weak cell–cell interactions, they can invade host tissues through a collective mode. Yet, how cancer cells without stable cell–cell junctions polarize collectively to migrate and invade is not fully understood. Here, using a wound-healing assay, we elucidate the polarization of carcinoma cells at the population level. We show that with loose intercellular connections, the highly polarized leader cells can induce the polarization of following cancer cells and subsequent transmission of polarity information by membrane protrusions, leading to gradient polarization at the monolayer boundary. Unlike the polarization of epithelial monolayer where Rac1/Cdc42 pathway functions primarily, our data show that collective polarization of carcinoma cells is predominantly controlled by Golgi apparatus, a disruption of which results in the destruction of collective polarization over a large scale. We reveal that the Golgi apparatus can sustain membrane protrusion formation, polarized secretion, intracellular trafficking, and F-actin polarization, which contribute to collective cancer cell polarization and its transmission between cells. These findings could advance our understanding of collective cancer invasion in tumors.

Ultralong recovery time in nanosecond electroporation systems enabled by orientational-disordering processes

“…85 Understanding collective dynamics of cancer development can lead to new strategies for cancer monitoring, which implies that traditional single cell-based studies may not be sufficient. 37,86,87 As a result, utilizing medium cell populations can not only enhance the understanding of cancer development, but also reduce intrinsic heterogeneity within the cell population. 88,89 This would improve the reliability of results in applications such as drug development, tumor characterization and other biological studies.…”

“…Moreover, disruption of the cell cytoskeleton caused by pulsed electric fields have been explored. [35][36][37] As the cytoskeleton is dynamically connected to the cell membrane, [38][39][40] the membrane permeability after electroporation and cell viability can be modified by the chemical or physical disruption of the cytoskeleton. 36,41 Furthermore, the elastic modulus of cells decreases after applying electric fields.…”

How Circulating Cancer Cells Disguise: the Role of Platelets

“…Platelets were released from the epithelial cells during overnight storage, making the CETCs accessible to the speci c antibody. The subsequent cap formation may be a particular characteristic of epithelial cells [23] and the joint movement of EpCAM on the tumor cells with the platelets is suggestive of a preferential binding of the platelets to EpCAM. Activation of platelets did not lead to thrombus formation due to the coagulation-inhibitory environment in this arti cial system.…”

Directional-to-random transition of cell cluster migration

“…[7][8][9][10][11][12][13] However, recent research has shed light on the cooperative role of physical cues present in the cellular environment in conjunction with chemical signals. [14][15][16][17][18] For instance, cells can perceive and migrate along gradients of substrate stiffness, [14] exhibiting collective movement through physical interactions, [15,16] and undergoing polarization within microconfinement. [17,18] Despite these advancements, the regulatory effects of crowding, which is a dominant environmental factor in tissues, remain relatively unexplored.…”