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Mechanics of a multilayer epithelium instruct tumor architecture and function

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE152488 | GEO | 2020/07/01

REPOSITORIES: GEO

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Mechanics of a multilayer epithelium instruct tumour architecture and function.

Project description:Loss of normal tissue architecture is a hallmark of oncogenic transformation1. In developing organisms, tissues architectures are sculpted by mechanical forces during morphogenesis2. However, the origins and consequences of tissue architecture during tumorigenesis remain elusive. In skin, premalignant basal cell carcinomas form 'buds', while invasive squamous cell carcinomas initiate as 'folds'. Here, using computational modelling, genetic manipulations and biophysical measurements, we identify the biophysical underpinnings and biological consequences of these tumour architectures. Cell proliferation and actomyosin contractility dominate tissue architectures in monolayer, but not multilayer, epithelia. In stratified epidermis, meanwhile, softening and enhanced remodelling of the basement membrane promote tumour budding, while stiffening of the basement membrane promotes folding. Additional key forces stem from the stratification and differentiation of progenitor cells. Tumour-specific suprabasal stiffness gradients are generated as oncogenic lesions progress towards malignancy, which we computationally predict will alter extensile tensions on the tumour basement membrane. The pathophysiologic ramifications of this prediction are profound. Genetically decreasing the stiffness of basement membranes increases membrane tensions in silico and potentiates the progression of invasive squamous cell carcinomas in vivo. Our findings suggest that mechanical forces-exerted from above and below progenitors of multilayered epithelia-function to shape premalignant tumour architectures and influence tumour progression.

| S-EPMC7787055 | biostudies-literature

Mechanics of a multilayer epithelium instruct tumor architecture and function [adult]

Project description:Loss of normal tissue architecture is a hallmark of oncogenic transformation. Mechanical forces sculpt tissue architectures during morphogenesis. However, their origins and consequences during tumorigenesis remain elusive. In skin, premalignant basal cell carcinomas (BCCs) form ‘buds’, while invasive squamous cell carcinomas (SCC) initiate as ‘folds’. Using computational modeling, genetic manipulations and biophysical measurements, we identify the biophysical underpinnings and biological consequences of these tumor architectures. Cell proliferation and actomyosin contractility dominate tissue architectures in monolayer, but not multilayer epithelia. In stratified epidermis, softening and enhanced remodeling of the basement membrane (BM) promote tumor budding, while BM stiffening promotes folding. We show that additional key forces stem from progenitor cell stratification and differentiation Tumor-specific suprabasal stiffness gradients are generated as oncogenic lesions progress toward malignancy, which we computationally predict alter extensile tensions on the tumor BM. The pathophysiologic ramifications of this prediction are profound. Genetically decreasing BM stiffness elevates BM tensions in silico and potentiates invasive SCC progression in vivo. Our findings suggest that mechanical forces, exerted from above and below progenitors of multilayered epithelia, are integrally linked and function to shape premalignant tumor architectures and influence tumor progression.

2020-07-01 | GSE152487 | GEO

Mechanics of a multilayer epithelium instruct tumor architecture and function [E15]

2020-07-01 | GSE152486 | GEO

Mechanics of a multilayer epithelium instruct tumor architecture and function

Project description:Mechanics of a multilayer epithelium instruct tumor architecture and function

| PRJNA639524 | ENA

Mechanics of a multilayer epithelium instruct tumor architecture and function [E15]

Project description:Mechanics of a multilayer epithelium instruct tumor architecture and function [E15]

| PRJNA639528 | ENA

Mechanics of a multilayer epithelium instruct tumor architecture and function [adult]

Project description:Mechanics of a multilayer epithelium instruct tumor architecture and function [adult]

| PRJNA639529 | ENA

Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity

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