Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Geometric Dependence of 3D Collective Cancer Invasion.

ABSTRACT: Metastasis of mesenchymal tumor cells is traditionally considered as a single-cell process. Here, we report an emergent collective phenomenon in which the dissemination rate of mesenchymal breast cancer cells from three-dimensional tumors depends on the tumor geometry. Combining experimental measurements and computational modeling, we demonstrate that the collective dynamics is coordinated by the mechanical feedback between individual cells and their surrounding extracellular matrix (ECM). We find the tissue-like fibrous ECM supports long-range physical interactions between cells, which turn geometric cues into regulated cell dissemination dynamics. Our results suggest that migrating cells in three-dimensional ECM represent a distinct class of an active particle system in which the collective dynamics is governed by the remodeling of the environment rather than direct particle-particle interactions.

SUBMITTER: Kim J

PROVIDER: S-EPMC7063428 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Geometric Dependence of 3D Collective Cancer Invasion.

Kim Jihan J Zheng Yu Y Alobaidi Amani A AA Nan Hanqing H Tian Jianxiang J Jiao Yang Y Sun Bo B

Biophysical journal 20200117 5

Metastasis of mesenchymal tumor cells is traditionally considered as a single-cell process. Here, we report an emergent collective phenomenon in which the dissemination rate of mesenchymal breast cancer cells from three-dimensional tumors depends on the tumor geometry. Combining experimental measurements and computational modeling, we demonstrate that the collective dynamics is coordinated by the mechanical feedback between individual cells and their surrounding extracellular matrix (ECM). We fi ...[more]

PMID: 32049055

Similar Datasets

Probing 3D Collective Cancer Invasion Using Double-Stranded Locked Nucleic Acid Biosensors.

Project description:Cancer is a leading cause of death worldwide and metastases are responsible for over 90% of human cancer deaths. There is an urgent need to develop novel therapeutics for suppressing cancer invasion, the initial step of metastasis. Nevertheless, the regulation of cancer invasion is poorly understood due to a paucity of tools for monitoring the invasion process in 3D microenvironments. Here, we report a double-stranded locked nucleic acid (dsLNA) biosensor for investigating 3D collective cancer invasion. By incorporating multiphoton microscopy and the dsLNA biosensor, we perform dynamic single cell gene expression analysis while simultaneously characterizing the biomechanical interaction between the invading sprouts and the extracellular matrix. Gene profiling of invasive leader cells and detached cells suggest distinctive signaling mechanisms involved in collective and individual invasion in the 3D microenvironment. Our results underscore the involvement of Notch signaling in 3D collective cancer invasion, which warrants further investigation toward antimetastasis therapy in the future.

| S-EPMC5488859 | biostudies-literature

Geometric decompositions of collective motion.

Project description:Collective motion in nature is a captivating phenomenon. Revealing the underlying mechanisms, which are of biological and theoretical interest, will require empirical data, modelling and analysis techniques. Here, we contribute a geometric viewpoint, yielding a novel method of analysing movement. Snapshots of collective motion are portrayed as tangent vectors on configuration space, with length determined by the total kinetic energy. Using the geometry of fibre bundles and connections, this portrait is split into orthogonal components each tangential to a lower dimensional manifold derived from configuration space. The resulting decomposition, when interleaved with classical shape space construction, is categorized into a family of kinematic modes-including rigid translations, rigid rotations, inertia tensor transformations, expansions and compressions. Snapshots of empirical data from natural collectives can be allocated to these modes and weighted by fractions of total kinetic energy. Such quantitative measures can provide insight into the variation of the driving goals of a collective, as illustrated by applying these methods to a publicly available dataset of pigeon flocking. The geometric framework may also be profitably employed in the control of artificial systems of interacting agents such as robots.

| S-EPMC5415679 | biostudies-literature

An epigenetically distinct breast cancer cell subpopulation promotes collective invasion

Project description:A distinct highly invasive subpopulation was identified in breast cancer cell lines. The molecular characteristics of these cells was investigated, revealing a set of genes whose high expression confers the ability to invade. Total RNA isolated from the invasive subpopulation from 2 cells lines was compared to total RNA isolated from 2 noninvasive populations.

2014-06-19 | E-GEOD-58643 | biostudies-arrayexpress

Probing three-dimensional collective cancer invasion with DIGME.

Project description:Multicellular pattern formation plays an important role in developmental biology, cancer metastasis and wound healing. While many physical factors have been shown to regulate these multicellular processes, the role of ECM micro-to-meso scale geometry has been poorly understood in 3D collective cancer invasion.We have developed a mechanical-based strategy, Diskoid In Geometrically Micropatterned ECM (DIGME). DIGME allows easy engineering of the shape of 3D tissue organoid, the mesoscale ECM heterogeneity, and the fiber alignment of collagen-based ECM all at the same time. We have employed DIGME to study the 3D invasion of MDA-MB-231 diskoids in engineered collagen matrix. We find that the collective cancer invasion is closely regulated by the micro-to-meso scale geometry of the ECM.We conclude that DIGME provides a simple yet powerful tool to probe 3D dynamics of tissue organoids in physically patterned microenvironments.

| S-EPMC5876692 | biostudies-other

A Geometric Representation of Collective Attention Flows.

Project description:With the fast development of Internet and WWW, "information overload" has become an overwhelming problem, and collective attention of users will play a more important role nowadays. As a result, knowing how collective attention distributes and flows among different websites is the first step to understand the underlying dynamics of attention on WWW. In this paper, we propose a method to embed a large number of web sites into a high dimensional Euclidean space according to the novel concept of flow distance, which both considers connection topology between sites and collective click behaviors of users. With this geometric representation, we visualize the attention flow in the data set of Indiana university clickstream over one day. It turns out that all the websites can be embedded into a 20 dimensional ball, in which, close sites are always visited by users sequentially. The distributions of websites, attention flows, and dissipations can be divided into three spherical crowns (core, interim, and periphery). 20% popular sites (Google.com, Myspace.com, Facebook.com, etc.) attracting 75% attention flows with only 55% dissipations (log off users) locate in the central layer with the radius 4.1. While 60% sites attracting only about 22% traffics with almost 38% dissipations locate in the middle area with radius between 4.1 and 6.3. Other 20% sites are far from the central area. All the cumulative distributions of variables can be well fitted by "S"-shaped curves. And the patterns are stable across different periods. Thus, the overall distribution and the dynamics of collective attention on websites can be well exhibited by this geometric representation.

| S-EPMC4556699 | biostudies-literature

Therapeutic Targeting of Collective Invasion in Ovarian Cancer.

Project description:Ovarian cancer is the seventh most commonly diagnosed cancer amongst women and has the highest mortality rate of all gynaecological malignancies. It is a heterogeneous disease attributed to one of three cell types found within the reproductive milieu: epithelial, stromal, and germ cell. Each histotype differs in etiology, pathogenesis, molecular biology, risk factors, and prognosis. Furthermore, the origin of ovarian cancer remains unclear, with ovarian involvement secondary to the contribution of other gynaecological tissues. Despite these complexities, the disease is often treated as a single entity, resulting in minimal improvement to survival rates since the introduction of platinum-based chemotherapy over 30 years ago. Despite concerted research efforts, ovarian cancer remains one of the most difficult cancers to detect and treat, which is in part due to the unique mode of its dissemination. Ovarian cancers tend to invade locally to neighbouring tissues by direct extension from the primary tumour, and passively to pelvic and distal organs within the peritoneal fluid or ascites as multicellular spheroids. Once at their target tissue, ovarian cancers, like most epithelial cancers including colorectal, melanoma, and breast, tend to invade as a cohesive unit in a process termed collective invasion, driven by specialized cells termed "leader cells". Emerging evidence implicates leader cells as essential drivers of collective invasion and metastasis, identifying collective invasion and leader cells as a viable target for the management of metastatic disease. However, the development of targeted therapies specifically against this process and this subset of cells is lacking. Here, we review our understanding of metastasis, collective invasion, and the role of leader cells in ovarian cancer. We will discuss emerging research into the development of novel therapies targeting collective invasion and the leader cell population.

| S-EPMC6471817 | biostudies-literature

Collective cancer cell invasion induced by coordinated contractile stresses.

Project description:The physical underpinnings of fibrosarcoma cell dissemination from a tumor in a surrounding collagen-rich matrix are poorly understood. Here we show that a tumor spheroid embedded in a 3D collagen matrix exerts large contractile forces on the matrix before invasion. Cell invasion is accompanied by complex spatially and temporally dependent patterns of cell migration within and at the surface of the spheroids that are fundamentally different from migratory patterns of individual fibrosarcoma cells homogeneously distributed in the same type of matrix. Cells display a continuous transition from a round morphology at the spheroid core, to highly aligned elongated morphology at the spheroid periphery, which depends on both ?1-integrin-based cell-matrix adhesion and myosin II/ROCK-based cell contractility. This isotropic-to-anisotropic transition corresponds to a shift in migration, from a slow and unpolarized movement at the core, to a fast, polarized and persistent one at the periphery. Our results also show that the ensuing collective invasion of fibrosarcoma cells is induced by anisotropic contractile stresses exerted on the surrounding matrix.

| S-EPMC4791242 | biostudies-literature

Collective cancer invasion forms an integrin-dependent radioresistant niche.

Project description:Cancer fatalities result from metastatic dissemination and therapy resistance, both processes that depend on signals from the tumor microenvironment. To identify how invasion and resistance programs cooperate, we used intravital microscopy of orthotopic sarcoma and melanoma xenografts. We demonstrate that these tumors invade collectively and that, specifically, cells within the invasion zone acquire increased resistance to radiotherapy, rapidly normalize DNA damage, and preferentially survive. Using a candidate-based approach to identify effectors of invasion-associated resistance, we targeted ?1 and ?V?3/?5 integrins, essential extracellular matrix receptors in mesenchymal tumors, which mediate cancer progression and resistance. Combining radiotherapy with ?1 or ?V integrin monotargeting in invading tumors led to relapse and metastasis in 40-60% of the cohort, in line with recently failed clinical trials individually targeting integrins. However, when combined, anti-?1/?V integrin dual targeting achieved relapse-free radiosensitization and prevented metastatic escape. Collectively, invading cancer cells thus withstand radiotherapy and DNA damage by ?1/?V?3/?5 integrin cross-talk, but efficient radiosensitization can be achieved by multiple integrin targeting.

| S-EPMC7037234 | biostudies-literature

Intravital microscopy of collective invasion plasticity in breast cancer.

Project description:Cancer invasion programs are adaptive by switching between metastatic collective and single-cell dissemination; however, current intravital microscopy models for epithelial cancer in mice fail to reliably recreate such invasion plasticity. Using microimplantation of breast cancer spheroids into the murine mammary fat pad and live-cell monitoring, we show microenvironmental conditions and cytoskeletal adaptation during collective to single-cell transition in vivo E-cadherin-expressing 4T1 and E-cadherin-negative MMT tumors both initiated collective invasion along stromal structures, reflecting invasion patterns in 3D organotypic culture and human primary ductal and lobular carcinoma. Collectively invading cells developed weakly oscillatory actin dynamics, yet provided zones for single-cell transitions with accentuated, more chaotic actin fluctuations. This identifies collective invasion in vivo as a dynamic niche and efficient source for single-cell release.

| S-EPMC6176993 | biostudies-literature

Intratumoral Heterogeneity Promotes Collective Cancer Invasion through NOTCH1 Variation.

Project description:Cellular and molecular heterogeneity within tumors has long been associated with the progression of cancer to an aggressive phenotype and a poor prognosis. However, how such intratumoral heterogeneity contributes to the invasiveness of cancer is largely unknown. Here, using a tumor bioengineering approach, we investigate the interaction between molecular subtypes within bladder microtumors and the corresponding effects on their invasiveness. Our results reveal heterogeneous microtumors formed by multiple molecular subtypes possess enhanced invasiveness compared to individual cells, even when both cells are not invasive individually. To examine the molecular mechanism of intratumoral heterogeneity mediated invasiveness, live single cell biosensing, RNA interference, and CRISPR-Cas9 gene editing approaches were applied to investigate and control the composition of the microtumors. An agent-based computational model was also developed to evaluate the influence of NOTCH1 variation on DLL4 expression within a microtumor. The data indicate that intratumoral variation in NOTCH1 expression can lead to upregulation of DLL4 expression within the microtumor and enhancement of microtumor invasiveness. Overall, our results reveal a novel mechanism of heterogeneity mediated invasiveness through intratumoral variation of gene expression.

| S-EPMC8619970 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data