Erik H J Danen | PubMed Health

PubMed2026

Informing agent-based models with spatial data using convolutional autoencoders.

MOTIVATION: Spatial computational models such as agent-based models (ABMs) offer powerful in silico tools to study tumor dynamics, yet imaging data are still rarely used to inform these models directly. RESULTS: We present an ABM optimization framework that leverages convolutional encoders to compare spatial patterns between experimental imaging data and ABM-generated outputs within a shared latent space. This quantitative comparison was used to estimate ABM parameters across three datasets, ranging from synthetic data to 3D tumoroid-T cell co-culture microscopy and histopathology images from The Cancer Genome Atlas skin cutaneous melanoma samples. Estimated parameters were evaluated using data-derived features and experimental knowledge, including experimental conditions and gene expressions. Simulations using optimized parameters reproduced key spatial features of the training images, such as tumor boundary complexity and tumor-tumor neighborhood structure. Together, these results demonstrate a flexible framework for ABM parameter optimization using spatial data across modalities, enabling systematic investigation of how spatial architecture influences tumor progression and immune interactions. AVAILABILITY AND IMPLEMENTATION: Source code is available at https://github.com/SysBioOncology/ AutoencoderABM under the GPL-3.0 license, with corresponding data sets at https://zenodo.org/records/19022344.

Autoencoder↗

PubMed2005

Integrins control motile strategy through a Rho-cofilin pathway.

During wound healing, angiogenesis, and tumor invasion, cells often change their expression profiles of fibronectin-binding integrins. Here, we show that beta1 integrins promote random migration, whereas beta3 integrins promote persistent migration in the same epithelial cell background. Adhesion to fibronectin by alpha(v)beta3 supports extensive actin cytoskeletal reorganization through the actin-severing protein cofilin, resulting in a single broad lamellipod with static cell-matrix adhesions at the leading edge. Adhesion by alpha5beta1 instead leads to the phosphorylation/inactivation of cofilin, and these cells fail to polarize their cytoskeleton but extend thin protrusions containing highly dynamic cell-matrix adhesions in multiple directions. The activity of the small GTPase RhoA is particularly high in cells adhering by alpha5beta1, and inhibition of Rho signaling causes a switch from a beta1- to a beta3-associated mode of migration, whereas increased Rho activity has the opposite effect. Thus, alterations in integrin expression profiles allow cells to modulate several critical aspects of the motile machinery through Rho GTPases.

Actin Cytoskeleton↗

PubMed2005

Integrins: regulators of tissue function and cancer progression.

Integrins are adhesion receptors that connect cells to components of the extracellular matrix or to counter receptors on other cells. Besides mediating stable adhesion, these receptors are implicated in the deposition of extracellular matrices and they are crucial for cell migration. Integrin-mediated adhesion also modulates signal transduction cascades downstream of other receptors and thereby regulates cell survival, proliferation, and the expression of differentiation-related genes. In this review, an overview of the evidence for roles of integrins in tissue development and function is given and the contribution of changes in integrin expression to cancer is discussed.

Animals↗

PubMed2003

Integrins in regulation of tissue development and function.

Cell adhesion is indispensable for embryonic development and for proper tissue function. In metazoans, integrins are the major adhesion receptors that connect cells to components of the extracellular matrix. Integrins are implicated in assembly of extracellular matrices, cell adhesion and migration on extracellular matrices, and in vertebrates (in which the integrin family has expanded) they can also mediate cell-cell adhesion. Furthermore, integrin-mediated adhesion can modulate many different signal transduction cascades and support cell survival, proliferation, and influence the expression of differentiation-related genes. In this review we briefly explain how integrins can affect so many different aspects of cell behavior and discuss evidence for roles of integrins in tissue development, function, and disease.

Animals↗

PubMed2003

Integrins in regulation of tissue development and function.

Cell adhesion is indispensable for embryonic development and for proper tissue function. In metazoans, integrins are the major adhesion receptors that connect cells to components of the extracellular matrix. Integrins are implicated in assembly of extracellular matrices, cell adhesion and migration on extracellular matrices, and in vertebrates (in which the integrin family has expanded) they can also mediate cell-cell adhesion. Furthermore, integrin-mediated adhesion can modulate many different signal transduction cascades and support cell survival, proliferation, and influence the expression of differentiation-related genes. In this review we briefly explain how integrins can affect so many different aspects of cell behavior and discuss evidence for roles of integrins in tissue development, function, and disease.

Animals↗

PubMed2002

The fibronectin-binding integrins alpha5beta1 and alphavbeta3 differentially modulate RhoA-GTP loading, organization of cell matrix adhesions, and fibronectin fibrillogenesis.

We have studied the formation of different types of cell matrix adhesions in cells that bind to fibronectin via either alpha5beta1 or alphavbeta3. In both cases, cell adhesion to fibronectin leads to a rapid decrease in RhoA activity. However, alpha5beta1 but not alphavbeta3 supports high levels of RhoA activity at later stages of cell spreading, which are associated with a translocation of focal contacts to peripheral cell protrusions, recruitment of tensin into fibrillar adhesions, and fibronectin fibrillogenesis. Expression of an activated mutant of RhoA stimulates alphavbeta3-mediated fibrillogenesis. Despite the fact that alpha5beta1-mediated adhesion to the central cell-binding domain of fibronectin supports activation of RhoA, other regions of fibronectin are required for the development of alpha5beta1-mediated but not alphavbeta3-mediated focal contacts. Using chimeras of beta1 and beta3 subunits, we find that the extracellular domain of beta1 controls RhoA activity. By expressing both beta1 and beta3 at high levels, we show that beta1-mediated control of the levels of beta3 is important for the distribution of focal contacts. Our findings demonstrate that the pattern of fibronectin receptors expressed on a cell dictates the ability of fibronectin to stimulate RhoA-mediated organization of cell matrix adhesions.

Actins↗