Cell adhesion and metastasis

Created by Abcam in collaboration with Jeroen Middelbeek

Normal epithelial tissue Proliferation Invasion Intravasation Capture by Extravasation Key

cell adhesion E-Cadherin

N-Cadherin

Integrin mediated
cell-matrix adhesions

B Sites of degradation

Matrix degrading
proteases
Epithelial (carcinoma) cells
C Selectins

CD44, CEA, PODCXL

A
ICAM1, VCAM1

Platelets

D E Inflammatory cells
Extracellular matrix Basal membrane Capture by Neutrophils
F
physical occlusion Growth factors (VEGF,
Histamine) and reactive
oxygen species

Vascular space Endothelial cells Blood flow G H

G
Secondary tumor
growth

Basal membrane I

Extravascular space

Epithelial Mesenchymal Collective Single cell Extracellular matrix degradation Intravasation Extravasation Secondary tumor growth

A B C D E F G H I
TWIST1/YAP/TAZ Actin and myosin contraction
Trailing edge:
Normal
– Adhesion
epithelial cell
Oncogenic transformation

dissolution
– Tail retraction
Directional migration

Proliferation
Migration

Leading edge:
Tumor – Adhesion
cell formation
– Degradation
– Protrusion
Matrix stiffness

Normal epithelial tissue Destabilization of cell-cell
architecture controlled by adhesion by internalization
contact-inhibition or reduced expression of
E-cadherin and increased
expression of N-cadherin
The rigidity of the surrounding tumor matrix influences Cell polarization, migration, Gelatinase enzymes such as MMP-2 Inflammation response Rolling through Arrest through Arrest through Vasoactive compounds Secondary tumors produce
tumor progression. Stiffer matrices infer nuclear localization and invasion and MMP-9 released by tumor cells, induces vascular permeability weak adhesive strong adhesive neutrophil secreted by tumor cells and growth factors such as VEGF
of mechanomediators (eg TWIST1 and YAP/TAZ) leading to degrade collagen found in the by affecting endothelial interactions interactions aggregation adhered platelets induce to promote the formation of
cytoskeleton remodeling during EMT basement membrane cell-cell adhesions vascular permeability new blood vessels
(angiogenesis)

Copyright © 2017 Abcam, All rights reserved. Based on a previous poster by Jeroen Middelbeek, Frank N van Leeuwen and Abcam.