posted on 2023-12-13, 21:07authored byLiu-Yuan Guan, Shao-Zhen Lin, Peng-Cheng Chen, Jian-Qing Lv, Bo Li, Xi-Qiao Feng
The interfacial interactions between
epithelia and cancer cells
have profound relevance for tumor development and metastasis. Through
monolayer confrontation of MCF10A (nontumorigenic human breast epithelial
cells) and MDA-MB-231 (human epithelial breast cancer cells) cells,
we investigate the epithelial–cancerous interfacial interactions
at the tissue level. We show that the monolayer interaction leads
to competitive interfacial morphodynamics and drives an intricate
spatial organization of MCF10A cells into multicellular finger-like
structures, which further branch into multiple subfinger-like structures.
These hierarchical interfacial structures penetrate the cancer monolayer
and can spontaneously segregate or even envelop cancer cell clusters,
consistent with our theoretical prediction. By tracking the substrate
displacements via embedded fluorescent nanobeads and implementing
nanomechanical modeling that combines atomic force microscopy and
finite element simulations, we computed mechanical force patterns,
including traction forces and monolayer stresses, caused by the monolayer
interaction. It is found that the heterogeneous mechanical forces
accumulated in the monolayers are able to squeeze cancer cells, leading
to three-dimensional interfacial bulges or cell extrusion, initiating
the p53 apoptosis signaling pathways of cancer cells. We reveal that
intercellular E-cadherin and P-cadherin of epithelial cells differentially
regulate the interfacial organization including migration speed, directionality,
spatial correlation, F-actin alignment, and subcellular protrusions
of MCF10A cells; whereas E-cadherin governs interfacial geometry that
is relevant to force localization and cancer cell extrusion, P-cadherin
maintains interfacial integrity that enables long-range force transmission.
Our findings suggest that the collaborative molecular and mechanical
behaviors are crucial for preventing epithelial tissues from undergoing
tumor invasion.