Figure 14.14c The Biology of Cancer (© Garland Science 2007)

E-cadherin and Beta-catenin signaling and metastasis

Rip-Tag transgenic

Mouse pancreatic

Cancer model

Green: cadherin

Red: catenin

Yellow-green area:

tumor in situ

Red area:

invasion front

Figure 14.14a The Biology of Cancer (© Garland Science 2007)

E-Cadherin stains strongly

in the core of a colon tumor. E-Cadherin stains lightly

at the edge of invasion front.

Figure 14.14b The Biology of Cancer (© Garland Science 2007)

Beta-catenin at membrane and cytoplasm

at the core of the tumor Beta-catenin in nuclei at the invasion front

Cadherin:cadherin interaction

and

Cadherin-beta-catenin signaling

Cell #1

Cell #2

Figure 14.14c The Biology of Cancer (© Garland Science 2007)

Beta-catenin signaling

Figure 14.15a The Biology of Cancer (© Garland Science 2007)

Twist induces EMT of MDCK cells and expression of EMT protein markers

Figure 14.15b The Biology of Cancer (© Garland Science 2007)

Figure 14.16a The Biology of Cancer (© Garland Science 2007)

Normal melanocyte

Express E-cad

Interact with

keratinocyte

Figure 14.16b The Biology of Cancer (© Garland Science 2007)

Melanoma cells:

Expreass N-cad

Interact with

Fibroblasts and

Endothelial cells

SCC-14 human pharyngeal

carcinoma xenograft tumor

Figure 14.19c The Biology of Cancer (© Garland Science 2007)

Transformed human

mammary epithelial cells

Implanted into SCID mouse

red

green

Transformed

human mammary

epithelial cells

implanted

xenograft tumor

OSCC

Brown:

P120 catenin

OSCC

Brown:

MMP2

Figure 14.19b The Biology of Cancer (© Garland Science 2007)

Invading tumor cells express EMT marker laminin-2r

Figure 14.17a The Biology of Cancer (© Garland Science 2007)

Colorectal carcinoma cells

Red: cytokeratin 18 green: basement membrane

GFP-labeld MMTV-PyMT tumor cells injected via tail vein

mesenchymal epithelial

metastatic cancer cells in lung

Figure 14.18 The Biology of Cancer (© Garland Science 2007)

Similarity in biomarker expression between primary and metastasized tumors

Figure 14.20a The Biology of Cancer (© Garland Science 2007)

TGF-beta induced EMT

Figure 14.20b The Biology of Cancer (© Garland Science 2007)

MET

Figure 14.20c The Biology of Cancer (© Garland Science 2007)

Figure 14.20d The Biology of Cancer (© Garland Science 2007)

Figure 14.20e The Biology of Cancer (© Garland Science 2007)

Detroit 562

carcinoma cells

Green:

TGF-beta

by stroma

Red:

Integrin by

cancer cells

Cancer-stroma

Feedback loop

Figure 14.21 The Biology of Cancer (© Garland Science 2007)

NF-kb signaling is needed for TGF-beta induced EMT markers

Figure 14.24 The Biology of Cancer (© Garland Science 2007)

HGF induced MDCK cells scattering

DKK1 & SFRP1:

Wnt signalimng

inhibitors

BMPs: EMT inhibitors

Figure 14.25 The Biology of Cancer (© Garland Science 2007)

Signaling pathways affecting EMT

Role of macrophage in metastasis

Figure 14.22a The Biology of Cancer (© Garland Science 2007)

Op/op: cannot make CSF-1 needed to recruit macrophages

Figure 14.22b The Biology of Cancer (© Garland Science 2007)

CSF -/- CSF +/-

CSF is essential for macrophages, which promote invasion.

MMTV-

Py-MT

Mouse

tumor

CSF:

Cancer

asso-

fibroblasts

Figure 14.22c The Biology of Cancer (© Garland Science 2007)

Ability of Py-MT tumor cells metastasize to lung with or without CSF-1

Figure 14.23a The Biology of Cancer (© Garland Science 2007)

Expression of complementary

molecules by cancer cells and

tumor asso-macrophages

Figure 14.23b The Biology of Cancer (© Garland Science 2007)

Macrophages promote breast cancer cells to move upward into collagen.

Figure 14.23c The Biology of Cancer (© Garland Science 2007)

Potent transcriptional factors that

Promote EMT