Upload
alejandro-morales-gomez
View
214
Download
0
Embed Size (px)
Citation preview
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 1/73
The Biology of Cancer First Edition
Chapter 14:
Moving Out:
Invasion and Metastasis
Copyright © Garland Science 2007
Robert A. Weinberg
Figure 14.1 The Biology of Cancer (© Garland Science 2007)
CT-PET fusion
image of
a lymphoma
patient
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 2/73
Figure 13.37 The Biology of Cancer (© Garland Science 2007)
Pancreas of Rip-Tag transgenic mouse (transgene of
SV40 large T and small T antigens)
The Rip-Tag model of islet cell tumor progression
Figure 14.2a The Biology of Cancer (© Garland Science 2007)
Endothelial cells
Metastatic islet cell tumor in a lymphatic channels
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 3/73
Figure 14.2b The Biology of Cancer (© Garland Science 2007)
Breast cancer cells in lymph node
Figure 14.2c The Biology of Cancer (© Garland Science 2007)
Metastatic cancer cells in bone marrow (Wright-Giemsa stain
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 4/73
Section 1.
Travel of cancer cells from aprimary tumor to a site of potentialmetastasis depends on a series ofcomplex biological steps
Figure 14.3 The Biology of Cancer (© Garland Science 2007)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 5/73
Figure 13.5a The Biology of Cancer (© Garland Science 2007)
The structure of
basement membrane
(specialized ECM)
Hemidesmosome is
composed of integrin
and laminin
Figure 13.5b The Biology of Cancer (© Garland Science 2007)
The structure of basement
membrane
Extra-cellular Matrix
(ECM) protein
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 6/73
Figure 14.4 The Biology of Cancer (© Garland Science 2007)
The invasion metastasis cascade: six steps are involved
Figure 14.5a The Biology of Cancer (© Garland Science 2007)
Lobular
carcinoma
of breast
Patterns of Invasion
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 7/73
Figure 14.5b The Biology of Cancer (© Garland Science 2007)
Red: E-cadherin, green: beta-1-integrin, blue: matrix
Melanoma cells
Figure 14.5c The Biology of Cancer (© Garland Science 2007)
Squamous cell carcinoma of cervix
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 8/73
Figure 13.39b The Biology of Cancer (© Garland Science 2007)
Figure 13.39a The Biology of Cancer (© Garland Science 2007)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 9/73
Figure 14.6 The Biology of Cancer (© Garland Science 2007)
Figure 14.7a The Biology of Cancer (© Garland Science 2007)
Intra-vital microscopy
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 10/73
Figure 14.7b The Biology of Cancer (© Garland Science 2007)
Intravital fluorescence microscopy
Green: plasma
Red: RBC
Figure 14.8 The Biology of Cancer (© Garland Science 2007)
Confocal microscopy
Green: rat fibrosarcoma cell
Red: LDL of the arteriole
5 days after injection of single cells injection into mouse vein
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 11/73
Figure 14.9 The Biology of Cancer (© Garland Science 2007)
Cancer cell push aside the
endothelial cells, reach
basement membrane
Diapedesis
Resolving of the thrombus
Extravasation
Section 2.
Colonization represents the mostcomplex and challenging step ofthe invasion-metastasis cascade
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 12/73
Figure 14.10a The Biology of Cancer (© Garland Science 2007)
Micro-metastasis in bone marrow: colon cancer
(anti-cytokeratin antibody stain)
Figure 14.10b The Biology of Cancer (© Garland Science 2007)
Micro-metastasis in bone marrow: breast cancer
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 13/73
Figure 14.10c The Biology of Cancer (© Garland Science 2007)
Two clusters of lung adenocarcinoma in the lymph node
Figure 14.11a, b The Biology of Cancer (© Garland Science 2007)
Genetic heterogeneity of micrometastasis and the evolution of
colonizing ability
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 14/73
Figure 14.11c The Biology of Cancer (© Garland Science 2007)
Figure 14.12 The Biology of Cancer (© Garland Science 2007)
Persistence of solitary dormant (冬眠) tumor cells many
weeks after introduction into the liver
Following isolation and in vitro culturing, the descendantsof many of these cells were tumorigenic
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 15/73
Section 3.
The epithelial-mesenchymaltransition and associated loss of E-cadherin expression enablecarcinoma cells to become invasive
Figure 14.13a The Biology of Cancer (© Garland Science 2007)
Embryogenesis and the epithelial-mesenchymal transition (EMT)
Sea urchin embryo
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 16/73
Figure 14.13b The Biology of Cancer (© Garland Science 2007)
Table 14.1 The Biology of Cancer (© Garland Science 2007)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 17/73
Figure 13.14 The Biology of Cancer (© Garland Science 2007)
The program of wound healing
Figure 13.13a The Biology of Cancer (© Garland Science 2007)
red: cytokeratin, green: vimentin
EMT was provoked by a 3-day-long exposure to MMP-3 , which
could initiate EMT through its ability to degrade E-cadherin.
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 18/73
Figure 13.13b The Biology of Cancer (© Garland Science 2007)
Green: actin
Red: cytokeratin
Individual cells may spontaneously have EMT,
suggesting the plasticity of these cells.
Figure 13.13c The Biology of Cancer (© Garland Science 2007)
The serial changes of a mono-layer of breast epithelial cells
after a patch of cells were removed.
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 19/73
Table 14.2 The Biology of Cancer (© Garland Science 2007)
Figure 14.14a The Biology of Cancer (© Garland Science 2007)
Immunohistochemical stain for E-cadherin
EMT at the invasive edge of a malignant tumor
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 20/73
Figure 14.14b The Biology of Cancer (© Garland Science 2007)
Immunohistochemical stain for β-catenin
Figure 14.14c The Biology of Cancer (© Garland Science 2007)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 21/73
Figure 13.12a The Biology of Cancer (© Garland Science 2007)
Figure 13.12b The Biology of Cancer (© Garland Science 2007)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 22/73
Figure 13.12c The Biology of Cancer (© Garland Science 2007)
Figure 13.12d The Biology of Cancer (© Garland Science 2007)
Immunofluorescence stain of Keratinocytes
Yellow: E-cadherin, red: actin
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 23/73
Figure 6.26a The Biology of Cancer (© Garland Science 2007)
Figure 14.16a The Biology of Cancer (© Garland Science 2007)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 24/73
Figure 14.16b The Biology of Cancer (© Garland Science 2007)
Table 7.1 part 1 of 2 The Biology of Cancer (© Garland Science 2007)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 25/73
Table 7.1 part 2 of 2 The Biology of Cancer (© Garland Science 2007)
Table 7.2 The Biology of Cancer (© Garland Science 2007)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 26/73
Figure 14.15a The Biology of Cancer (© Garland Science 2007)
The EMT can be induced by several transcriptional factors
Example: Twist on canine kidney cells
Figure 14.15b The Biology of Cancer (© Garland Science 2007)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 27/73
Section 4.
The epithelial-mesenchymaltransition is often induced bystromal signals
Figure 14.17a The Biology of Cancer (© Garland Science 2007)
Reversibility of EMT:
Release of degradative enzymes, such as MMPs, is noted in EMT.
EMT may be triggered by the signals from the tumor associated stroma
Red: CK18
Green: basement membrane
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 28/73
Figure 14.17b The Biology of Cancer (© Garland Science 2007)
Figure 14.18 The Biology of Cancer (© Garland Science 2007)
The reversibility of EMT explains the peculiarity of many
metastasis: they are similar to the primary tumor
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 29/73
Figure 14.19a The Biology of Cancer (© Garland Science 2007)
Manifestation of EMT at the interface between tumor
epithelium and stroma
Figure 14.19b The Biology of Cancer (© Garland Science 2007)
Laminin-2γ
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 30/73
Figure 14.19c The Biology of Cancer (© Garland Science 2007)
Figure 14.19d The Biology of Cancer (© Garland Science 2007)
Vimentin
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 31/73
Figure 14.20a The Biology of Cancer (© Garland Science 2007)
Abudant evidence indicates that TGF-β is an important agent
for conveying these stromal signals
Figure 14.20b The Biology of Cancer (© Garland Science 2007)
Control of the EMT by TGF-β and its effect on tumorigenic cells
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 32/73
Figure 14.20c The Biology of Cancer (© Garland Science 2007)
Figure 14.20d The Biology of Cancer (© Garland Science 2007)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 33/73
Figure 14.20e The Biology of Cancer (© Garland Science 2007)
Figure 14.21 The Biology of Cancer (© Garland Science 2007)
NF-kB signaling was necessary for EMT in the EpRas cell line
TNF-α and TGF-β contribute to active NF-kB signaling
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 34/73
Figure 13.24 The Biology of Cancer (© Garland Science 2007)
Transgenic mice model
TAM(+) TAM (-)
Colony stimulating factor -1 (CSF-1) for recruit tumor associated macrophages
(TAM)
The effect of stromal macrophages on the invasive and metastatic
behavior of cancer cells
Figure 14.22a The Biology of Cancer (© Garland Science 2007)
Colony stimulating factor -1 (CSF-1) for recruit tumor
associated macrophages (TAM)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 35/73
Figure 14.22b The Biology of Cancer (© Garland Science 2007)
Figure 14.22c The Biology of Cancer (© Garland Science 2007)
Metastasis in the lung increase with age in the CSF-1(+) mice
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 36/73
Figure 14.23a The Biology of Cancer (© Garland Science 2007)
Figure 14.23b The Biology of Cancer (© Garland Science 2007)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 37/73
Figure 14.23c The Biology of Cancer (© Garland Science 2007)
Since macrophages are often found in close to microvessels,
the stimulation by tumor associated macrophages (TAM) may
also contribute to cancer cell intravasation
Figure 14.24 The Biology of Cancer (© Garland Science 2007)
Cell scattering and invasive behavior induced by
hepatocyte growth factor (HGF) or SF
HGF is another ligand of stromal origin, which is also capable of
inducing EMT in the epithelial cells trough the effect of Met protein
(HGF receptor)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 38/73
Figure 14.25 The Biology of Cancer (© Garland Science 2007)
Signals that triggered EMT
Section 5.
EMTs are programmed bytranscription factors that orchestratekey steps of embryogenesis
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 39/73
Table 14.3 The Biology of Cancer (© Garland Science 2007)
Figure 14.26a The Biology of Cancer (© Garland Science 2007)
Embryonic transcriptional factors programing EMT
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 40/73
Figure 14.26b The Biology of Cancer (© Garland Science 2007)
Figure 14.26c The Biology of Cancer (© Garland Science 2007)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 41/73
Figure 14.26d The Biology of Cancer (© Garland Science 2007)
Figure 14.26e The Biology of Cancer (© Garland Science 2007)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 42/73
Figure 14.26f The Biology of Cancer (© Garland Science 2007)
Figure 14.27 The Biology of Cancer (© Garland Science 2007)
Slug
transcription
factor in
wound
healing
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 43/73
Figure 14.28a The Biology of Cancer (© Garland Science 2007)
Slug suppress E-cadherin transcription
Expression of EMT-inducing embryonic transcription factors in human tumors
Figure 14.28b The Biology of Cancer (© Garland Science 2007)
Expression of EMT-inducing embryonic transcription factors in human tumors
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 44/73
Figure 14.28c The Biology of Cancer (© Garland Science 2007)
Expression of EMT-inducing embryonic transcription factors in human tumors
Figure 14.29a The Biology of Cancer (© Garland Science 2007)
Embryonic transcription factors and tumor progression
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 45/73
Figure 14.29b The Biology of Cancer (© Garland Science 2007)
Embryonic transcription factors and tumor progression
Figure 14.30 The Biology of Cancer (© Garland Science 2007)
Similarities
between EMT
signaling
during
embryogenesis
and tumor
progression
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 46/73
Figure 14.31a The Biology of Cancer (© Garland Science 2007)
Mammary carcinoma arising from transgenic MMTV-polyoma T mice
Matrix metalloproteinases (MMPs) produced by tumor associated cells, would
generate a halo of proteolysis (right figure)
Figure 14.31b The Biology of Cancer (© Garland Science 2007)
Red: fibroblast
Green: degraded
collagen IV
The ability of tumor cells to degrade collagen IV fibers
trough interaction with fibroblasts
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 47/73
Figure 14.31c The Biology of Cancer (© Garland Science 2007)
Elevated MMP-2imparted increased
invasiveness to the
breast cancer cells
Macrophages are important source of MMPs
Section 6.
Extracellular proteases play keyroles in invasiveness
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 48/73
Table 13.1 The Biology of Cancer (© Garland Science 2007)
Figure 13.25a The Biology of Cancer (© Garland Science 2007)
Tumor-
associated
macrophages
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 49/73
Figure 13.25b The Biology of Cancer (© Garland Science 2007)
VEGF expression in TAMVEGF expression in tumor cells
Figure 13.25c The Biology of Cancer (© Garland Science 2007)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 50/73
Figure 13.25d The Biology of Cancer (© Garland Science 2007)
TAM with expression of MMP-9, a key enzyme in
angiogenesis and invasiveness.
Figure 13.26 The Biology of Cancer (© Garland Science 2007)
Contribution of macrophages to tumorigenesis
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 51/73
Figure 14.32 The Biology of Cancer (© Garland Science 2007)
Podosomes are small, focal protrusions from the cell surface, that
are used to degrade the extracellular matrix (ECM) of immediate
vicinity. In cancer cells, they can also be called as invadosomes
Red: actin, green: ECM protein
Figure 14.33 The Biology of Cancer (© Garland Science 2007)
Ectopic expression of MMP-3 and mammary tumor progression
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 52/73
Figure 14.34 The Biology of Cancer (© Garland Science 2007)
uPA: urokinase
plasminogen
activator
Activation of extracellular proteins: MMPs and TGF-β by uPA and uPAR
Section 7.
Small Ras-like GTPases controlcellular processes includingadhesion,cell shape,and cell motility
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 53/73
Figure 14.35 The Biology of Cancer (© Garland Science 2007)
Figure 14.36a The Biology of Cancer (© Garland Science 2007)
Lamellipodia of rat liver cells
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 54/73
Figure 14.36b The Biology of Cancer (© Garland Science 2007)
Lamellipodia of a fibroblast
Red: actin Green:Ena protein
Figure 14.36c The Biology of Cancer (© Garland Science 2007)
Fish keratinocytes with prominent lamellipodia. EM demonstrate
densely woven network of actin filaments to extend the
lamellipodia in the direction of movement.
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 55/73
Figure 14.36d The Biology of Cancer (© Garland Science 2007)
Breast cancer cells Green: actin
The addition of heregulin induce the development of
lamellipodia that faces all directions
Figure 14.37a The Biology of Cancer (© Garland Science 2007)
Filopodia
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 56/73
Figure 14.37b The Biology of Cancer (© Garland Science 2007)
The leading edges of lamellipodia are ofteninterspersed with filopodia
Figure 14.37c The Biology of Cancer (© Garland Science 2007)
The actin fibers within a filopodium
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 57/73
Figure 14.38 The Biology of Cancer (© Garland Science 2007)
Effects of Rho-like proteins on the actin cytoskeleton and cell adhesion
Figure 14.38a The Biology of Cancer (© Garland Science 2007)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 58/73
Figure 14.38b The Biology of Cancer (© Garland Science 2007)
Figure 14.38c The Biology of Cancer (© Garland Science 2007)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 59/73
Figure 14.38d The Biology of Cancer (© Garland Science 2007)
Figure 14.39 The Biology of Cancer (© Garland Science 2007)
The circuitry
mediating EGF-induced cell
motility
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 60/73
Figure 14.40 The Biology of Cancer (© Garland Science 2007)
Influence of RhoC on metastasis
Section 8.
Metastasizing cells can uselymphatic vessels to disperse fromthe primary tumor
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 61/73
Figure 14.41a The Biology of Cancer (© Garland Science 2007)
Draining lymph nodes of the mammary glands
Figure 14.41b The Biology of Cancer (© Garland Science 2007)
Detection of sentinal lymph node by injection of a blue dye
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 62/73
Figure 14.41c The Biology of Cancer (© Garland Science 2007)
Figure 14.41d The Biology of Cancer (© Garland Science 2007)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 63/73
Section 9.
A variety of factors govern theorgan sites in which disseminatedcancer cells form metastases
Figure 14.42 The Biology of Cancer (© Garland Science 2007)
Primary tumors and their metastatic tropisms
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 64/73
Figure 14.44 The Biology of Cancer (© Garland Science 2007)
Section 10.
Metastasis to bone requires thesubversion of osteoblasts andosteoclasts
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 65/73
Figure 14.45a The Biology of Cancer (© Garland Science 2007)
Bone degradation by osteoclasts
Figure 14.45b The Biology of Cancer (© Garland Science 2007)
An osteoclast has excavated a shallow pit, which
revealed the complex meshwork of the bone matrix.
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 66/73
Figure 14.45c The Biology of Cancer (© Garland Science 2007)
Osteolytic lesion by tumor metastasis (scanning EM)
Figure 14.46 The Biology of Cancer (© Garland Science 2007)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 67/73
Figure 14.47 The Biology of Cancer (© Garland Science 2007)
osteoprotegerin
The physiologic balance between bone formation and resorption
Figure 14.48 The Biology of Cancer (© Garland Science 2007)
The bone matrix
is a rich source of
mitogenic and
trophic factors
Parathyroid hormone
related peptides
The vicious cycle of osteolytic metastasis
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 68/73
Figure 14.49 The Biology of Cancer (© Garland Science 2007)
MDA-MB-231is a breast cancer cell line usually produce osteolytic metastasis.
TGF-β stimulates osteolytic activity by forcing the breast cancer cells to
release PTHrP, which activate osteoblasts, then--- osteoclasts.
Section 11.
Metastasis suppressor genescontribute to regulating themetastatic phenotype
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 69/73
Table 14.4 The Biology of Cancer (© Garland Science 2007)
Section 12.
Occult micrometastases threatenthe long-term survival of cancerpatients
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 70/73
Figure 14.50a The Biology of Cancer (© Garland Science 2007)
Figure 14.50b The Biology of Cancer (© Garland Science 2007)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 71/73
Figure 14.51a The Biology of Cancer (© Garland Science 2007)
Use of expression array to predic disease progression
Figure 14.51b The Biology of Cancer (© Garland Science 2007)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 72/73
Figure 14.52a The Biology of Cancer (© Garland Science 2007)
Gene similarity between primary tumors and derived metastasis
Figure 14.52b The Biology of Cancer (© Garland Science 2007)
8/22/2019 capitulo de biolgia del cancer
http://slidepdf.com/reader/full/capitulo-de-biolgia-del-cancer 73/73
Figure 14.53 The Biology of Cancer (© Garland Science 2007)
Some expressed genes within tumor cells facilitate
specific types of metastasis
The End