Deficient cell-cell cohesion is linked with lobular localization in simplified models of lobular carcinomain situ(LCIS) DOI Creative Commons
Matthias Christgen, Rodrigo de Oliveira Caetano, Michael Eisenburger

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 14, 2024

Abstract Lobular carcinoma in situ (LCIS) is a precursor of invasive lobular the breast. LCIS cells lack cell-cell cohesion due to loss E-cadherin. grow mammary lobules rather than ducts. The etiology this pattern, especially its dependence on cellular cohesion, incompletely understood. We simulated passive intra-glandular scattering (CIS) an ultra-simplified hollow mold tissue replica (HMTR) and discrete-time mathematical model featuring particles variable sizes representing single (LCIS-like particles) or groups cohesive (DCIS-like particles). HMTR features structures reminiscent duct with associated lobules. discrete characterizes spatial redistribution over time includes transition probabilities between ductal localizations. Redistribution converged toward equilibrium depending particle size. Strikingly, proportions depended properties, which we also confirm continuous-time that considers controlling properties such as crowding. Particles increasing size, CIS proficient showed increasingly higher proportions. Our investigations represent two conceptual abstractions implying link localization LCIS, provide much-needed logical foundation for studying connections collective cell behavior cancer development breast tissues. In light findings from our simplified modeling approach, discuss multiple avenues near-future research can address evaluate hypothesis mathematically empirically.

Language: Английский

Spatial Engineering of Mammary Epithelial Cell Cultures with 3D Bioprinting Reveals Growth Control by Branch Point Proximity DOI Creative Commons
Leena M. Koskinen,

Lari Nieminen,

Antti Arjonen

et al.

Journal of Mammary Gland Biology and Neoplasia, Journal Year: 2024, Volume and Issue: 29(1)

Published: Feb. 28, 2024

Abstract The three-dimensional (3D) structure of the ductal epithelium and surrounding extracellular matrix (ECM) are integral aspects breast tissue, they have important roles during mammary gland development, function malignancy. However, architecture branched epithelial network is poorly recapitulated in current vitro models. 3D bioprinting an emerging approach to improve tissue-mimicry cell culture. Here, we developed optimized a protocol for normal cancerous cells into Y-shape study role positioning regulation proliferation invasion. Non-cancerous formed continuous networks with several organotypic features, whereas carcinoma situ (DCIS) –like cancer exhibited aberrant basal polarization defective formation basement membrane (BM). Quantitative analysis over time demonstrated that both proliferate more at branch tips compared trunk region 3D-bioprinted cultures, particularly tip further away from point. location-specific rate was independent TGFβ signaling but invasion DCIS-like reduced upon inhibition TGFβ. Thus, our data demonstrate can sense their position tips, thus recapitulating this feature branching morphogenesis. In all, results capacity method quantitative relationships between tissue behavior morphogenesis cancer.

Language: Английский

Citations

4
15th Annual ENBDC Meeting: How do Cellular Potency, Microenvironment and Natural Rhythms Influence Mammary Gland Biology and Breast Cancer? DOI Creative Commons
Maria Rafaeva, Beata Kaczyńska, Jaime Redondo-Pedraza

et al.

Journal of Mammary Gland Biology and Neoplasia, Journal Year: 2024, Volume and Issue: 29(1)

Published: Nov. 25, 2024

Following previous editions, the fifteenth annual workshop of European Network for Breast Development and Cancer (ENBDC) on Methods in Mammary Gland Biology was held from 2nd to 4th May Weggis, Switzerland. Over course this meeting, participants followed discussed presentations a roster internationally renowned invited speakers selected abstracts, complemented with two poster sessions covering exciting unpublished results. The covered projects normal mammary gland development, breast cancer evolution metastasis, as well epigenetic metabolic regulation cancer. As last year, early career researchers (ECR) hosted pre-workshop day, when stage provided allow PhD students postdocs showcase their results, they had ample time discussions experimental settings planning, while interacting several guests.

Language: Английский

Citations

1
Deficient cell-cell cohesion is linked with lobular localization in simplified models of lobular carcinoma in situ (LCIS) DOI Creative Commons
Matthias Christgen,

Rodrigo A Caetano,

Michael Eisenburger

et al.

Mathematical Biosciences, Journal Year: 2024, Volume and Issue: unknown, P. 109369 - 109369

Published: Dec. 1, 2024

Language: Английский

Citations

0
Deficient cell-cell cohesion is linked with lobular localization in simplified models of lobular carcinomain situ(LCIS) DOI Creative Commons
Matthias Christgen, Rodrigo de Oliveira Caetano, Michael Eisenburger

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 14, 2024

Abstract Lobular carcinoma in situ (LCIS) is a precursor of invasive lobular the breast. LCIS cells lack cell-cell cohesion due to loss E-cadherin. grow mammary lobules rather than ducts. The etiology this pattern, especially its dependence on cellular cohesion, incompletely understood. We simulated passive intra-glandular scattering (CIS) an ultra-simplified hollow mold tissue replica (HMTR) and discrete-time mathematical model featuring particles variable sizes representing single (LCIS-like particles) or groups cohesive (DCIS-like particles). HMTR features structures reminiscent duct with associated lobules. discrete characterizes spatial redistribution over time includes transition probabilities between ductal localizations. Redistribution converged toward equilibrium depending particle size. Strikingly, proportions depended properties, which we also confirm continuous-time that considers controlling properties such as crowding. Particles increasing size, CIS proficient showed increasingly higher proportions. Our investigations represent two conceptual abstractions implying link localization LCIS, provide much-needed logical foundation for studying connections collective cell behavior cancer development breast tissues. In light findings from our simplified modeling approach, discuss multiple avenues near-future research can address evaluate hypothesis mathematically empirically.

Language: Английский

Citations

0