Figure 13.2 The Biology of Cancer (© Garland Science 2007)

Hodgkins Lymphoma – A Cancer in Which 99% of the Tumor Cells Are Not Cancer Cells

Most Tumors Contain a Significant Fraction of Nontumor Cells

Most tumors are tissues that contain collaborating communites of tumor and nontumor cells

The best model for the formation of tumor tissues comes from studies of wound healing.

In many cases, a solid tumor behaves like a wound that does not heal.

Figure 13.14 The Biology of Cancer (© Garland Science 2007)

Platelets enmeshed in Fibrin clot

The Biology of Wound Healing

Figure 13.5b The Biology of Cancer (© Garland Science 2007)

Figure 13.10 The Biology of Cancer (© Garland Science 2007)

Many Cellular & Molecular Factors Are Involved in the Process of Wound Healing

Signals From Stromal Cells

Figure 13.18a The Biology of Cancer (© Garland Science 2007)

Figure 13.20 The Biology of Cancer (© Garland Science 2007)

Figure 13.19 The Biology of Cancer (© Garland Science 2007)

Angiogeneis & Its Critical Role in Tumor Growth

Adapted from: Principles of Cancer Biology 2006 By L. J. Kleinsmith

Progressive vascularization of tumor produced by implanted human colorectal cancer cells in mice.

Early Demonstrations of the Dependence of Tumors on Angiogenesis

The Angiogenic “Switch” -- A Balance of Factors

Figure 13.27d The Biology of Cancer (© Garland Science 2007)

However, low O2 promotes activation of HIF-1 (hypoxia inducible transcription factor). The targets of this gene include key angiogenesis factors, PDGF and others.

Limited Oxygen as Distance to Blood Vessels Increases

Figure 7.28a The Biology of Cancer (© Garland Science 2007)

The Von Hippel Landau tumor Suppressor and HIF-1

Figure 13.22b The Biology of Cancer (© Garland Science 2007)

CAFs in VIVO

CAFs & Vascularization

ECs & Cappilary Formation

Figure 13.6d The Biology of Cancer (© Garland Science 2007)

Endothelial Cells, PDGF, ECM & Pericytes Collaborate to Form Blood Vessels

Figure 13.25c The Biology of Cancer (© Garland Science 2007)

MMP-producing Stromal TAMs in Human Colorectal Cancer

TAMs & Angiogenesis

Figure 13.26 The Biology of Cancer (© Garland Science 2007)

Schematic Overview of TAM Support of Tumor Growth and Survival

Figure 13.37 The Biology of Cancer (© Garland Science 2007)

The Rip-Tag Model

Generation of transgenic mice in which Large T antigen and Small T antigen are placed under the insulin promoter yields animals that develop pancreatic tumors that are restricted to the β-islets.

Tumor Vasculature is Less Well Organized Than Normal Vasculature

Using Intravital Microscopy in Normal Tissue

In Rip-Tag Mice

The neovasculature of tumors is leaky

Figure 13.38b The Biology of Cancer (© Garland Science 2007)

Figure 13.42b The Biology of Cancer (© Garland Science 2007)

Angiogenesis, Disease Progression and Survival

Figure 13.45a The Biology of Cancer (© Garland Science 2007)

Figure 13.47a The Biology of Cancer (© Garland Science 2007)

Figure 13.47c,d The Biology of Cancer (© Garland Science 2007)

Figure 13.47e The Biology of Cancer (© Garland Science 2007)

Figure 13.47f The Biology of Cancer (© Garland Science 2007)

Figure 13.48a, b The Biology of Cancer (© Garland Science 2007)

Figure 13.48c The Biology of Cancer (© Garland Science 2007)

Figure 13.49 The Biology of Cancer (© Garland Science 2007)

Table 13.4 The Biology of Cancer (© Garland Science 2007)

Figure 13.12a The Biology of Cancer (© Garland Science 2007)