Defining the Hallmarks of Metastasis DOI Open Access
Danny R. Welch, Douglas R. Hurst

Cancer Research, Journal Year: 2019, Volume and Issue: 79(12), P. 3011 - 3027

Published: May 3, 2019

Abstract Metastasis is the primary cause of cancer morbidity and mortality. The process involves a complex interplay between intrinsic tumor cell properties as well interactions cells multiple microenvironments. outcome development nearby or distant discontiguous secondary mass. To successfully disseminate, metastatic acquire in addition to those necessary become neoplastic. Heterogeneity mechanisms involved, routes dissemination, redundancy molecular pathways that can be utilized, ability piggyback on actions surrounding stromal makes defining hallmarks metastasis extraordinarily challenging. Nonetheless, this review identifies four distinguishing features are required: motility invasion, modulate site local microenvironments, plasticity, colonize tissues. By these first principles metastasis, we provide means for focusing efforts aspects will improve patient outcomes.

Language: Английский

Extracellular matrix structure DOI
Achilleas D. Theocharis, Spyros S. Skandalis, Chrysostomi Gialeli

et al.

Advanced Drug Delivery Reviews, Journal Year: 2015, Volume and Issue: 97, P. 4 - 27

Published: Nov. 10, 2015

Language: Английский

Citations

2061

Mechanotransduction and extracellular matrix homeostasis DOI
Jay D. Humphrey, Eric R. Dufresne, Martin A. Schwartz

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2014, Volume and Issue: 15(12), P. 802 - 812

Published: Oct. 22, 2014

Language: Английский

Citations

1817

Concepts of extracellular matrix remodelling in tumour progression and metastasis DOI Creative Commons
Juliane Winkler, Abisola Abisoye-Ogunniyan, Kevin J. Metcalf

et al.

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Oct. 9, 2020

Abstract Tissues are dynamically shaped by bidirectional communication between resident cells and the extracellular matrix (ECM) through cell-matrix interactions ECM remodelling. Tumours leverage remodelling to create a microenvironment that promotes tumourigenesis metastasis. In this review, we focus on how tumour tumour-associated stromal deposit, biochemically biophysically modify, degrade ECM. These tumour-driven changes support growth, increase migration of cells, remodel in distant organs allow for metastatic progression. A better understanding underlying mechanisms tumourigenic is crucial developing therapeutic treatments patients.

Language: Английский

Citations

1599

Microenvironmental regulation of tumour angiogenesis DOI
Michele De Palma,

Daniela Biziato,

Tatiana V. Petrova

et al.

Nature reviews. Cancer, Journal Year: 2017, Volume and Issue: 17(8), P. 457 - 474

Published: July 14, 2017

Language: Английский

Citations

1537

Turning foes to friends: targeting cancer-associated fibroblasts DOI
Xueman Chen, Erwei Song

Nature Reviews Drug Discovery, Journal Year: 2018, Volume and Issue: 18(2), P. 99 - 115

Published: Nov. 23, 2018

Language: Английский

Citations

1441

CD8+ cytotoxic T lymphocytes in cancer immunotherapy: A review DOI
Bagher Farhood, Masoud Najafi, Keywan Mortezaee

et al.

Journal of Cellular Physiology, Journal Year: 2018, Volume and Issue: 234(6), P. 8509 - 8521

Published: Nov. 22, 2018

CD8+ cytotoxic T lymphocytes (CTLs) are preferred immune cells for targeting cancer. During cancer progression, CTLs encounter dysfunction and exhaustion due to immunerelated tolerance immunosuppression within the tumor microenvironment (TME), with all favor adaptive immune-resistance. Cancer-associated fibroblasts (CAFs), macrophage type 2 (M2) cells, regulatory (Tregs) could make immunologic barriers against CD8 + cell-mediated antitumor responses. Thus, needed be primed activated toward effector in a process called immunity cycle making durable efficient The cell priming is directed essentially as corroboration work between of innate including dendritic (DCs) natural killer (NK) CD4 adoptive immunity. Upon activation, infiltrate core or invading site (so-called infiltrated-inflamed [I-I] TME) take essential roles killing cells. Exogenous reactivation and/or can possible using rational immunotherapy strategies. increase ratio costimulatory coinhibitory mediators checkpoint blockade (ICB) approach. Programmed death-1 receptor (PD-1)-ligand (PD-L1) CTL-associated antigen 4 (CTLA-4) receptors that targeted relieving renewing their priming, respectively, thereby eliminating antigen-expressing Due diverse relation Tregs, Treg activity dampened increasing number rescuing functional potential induce immunosensitivity

Language: Английский

Citations

1326

Extracellular matrix assembly: a multiscale deconstruction DOI
Janna K. Mouw, Guanqing Ou, Valerie M. Weaver

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2014, Volume and Issue: 15(12), P. 771 - 785

Published: Nov. 5, 2014

Language: Английский

Citations

1301

Three-Dimensional in Vitro Cell Culture Models in Drug Discovery and Drug Repositioning DOI Creative Commons
Sigrid A. Langhans

Frontiers in Pharmacology, Journal Year: 2018, Volume and Issue: 9

Published: Jan. 22, 2018

Drug development is a lengthy and costly process that proceeds through several stages from target identification to lead discovery optimization, preclinical validation clinical trials culminating in approval for use. An important step this high-throughput screening (HTS) of small compound libraries identification. Currently, the majority cell-based HTS being carried out on cultured cells propagated two-dimensions (2D) plastic surfaces optimized tissue culture. At same time, compelling evidence suggests these non-physiological conditions are not representative residing complex microenvironment tissue. This discrepancy thought be significant contributor high failure rate drug discovery, where only low percentage drugs investigated ever make it gamut testing market. Thus, three-dimensional (3D) cell culture technologies more closely resemble vivo environments now pursued with intensity as they expected accommodate better precision discovery. Here we will review common approaches 3D culture, discuss significance cultures resistance repositioning address some challenges applying

Language: Английский

Citations

1291

Is It Time to Start Transitioning From 2D to 3D Cell Culture? DOI Creative Commons
Caleb Jensen, Yong Teng

Frontiers in Molecular Biosciences, Journal Year: 2020, Volume and Issue: 7

Published: March 6, 2020

Cell culture is an important and necessary process in drug discovery, cancer research, as well stem cell research. Most cells are currently cultured using two-dimensional (2D) methods, but new improved methods that implement three-dimensional (3D) techniques suggest compelling evidence much more advanced experiments can be performed. When performing 3D experiments, the environment manipulated to mimic of a vivo provide accurate data about cell-to-cell interactions, tumor characteristics, metabolic profiling, other types diseases. Scaffold based such hydrogel-based support, polymeric hard material-based hydrophilic glass fiber, organoids employed, each provides its own advantages applications. Likewise, there also scaffold-free used hanging drop microplates, magnetic levitation, spheroid microplates with ultra-low attachment coating. has potential alternative ways study organ behavior via use expected eventually bridge gap between 2D animal models. The present review compares culture, details surrounding different techniques, focuses on future applications culture.

Language: Английский

Citations

1232

Hepatic stellate cells as key target in liver fibrosis DOI Creative Commons

Takaaki Higashi,

Scott L. Friedman, Yujin Hoshida

et al.

Advanced Drug Delivery Reviews, Journal Year: 2017, Volume and Issue: 121, P. 27 - 42

Published: May 12, 2017

Language: Английский

Citations

1204