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Chapter 3

Chapter 3 . How Cancers Spread?. Metastasis. Metastases are formed by cancer cells that have left the primary tumor and traveled to a distant location. Lymphatic system Blood Certain types of cancer have a higher probability of metastasizing. Metastatic Carcinoma Cells. Risk of Metastasis.

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Chapter 3

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  1. Chapter 3 How Cancers Spread?

  2. Metastasis • Metastases are formed by cancer cells that have left the primary tumor and traveled to a distant location. • Lymphatic system • Blood • Certain types of cancer have a higher probability of metastasizing.

  3. Metastatic Carcinoma Cells

  4. Risk of Metastasis

  5. Invasion

  6. How Do Tumor Cell Grow? • Angiogenesis = growth and proliferation of endothelial cells that line the inner surface of existing blood vessels. • Normal Physiology of angiogenesis. • Angiogenesis is needed for tumor survival. From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.

  7. Tumor Angiogenesis. From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.

  8. Tumor Angiogenesis • Do Tumors Need a blood supply to survive? • Experiments by Judith Folkman in the early 1970 support the importance of angiogenesis. From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.

  9. Tumor Angiogenesis • Activators and Inhibitors regulate angiogeneis. • Cancer cells produce angiogenesis activators. • What molecules are capable of stimulating angiogenesis? • Epidermal GF • TNF-a • PDGF • IL-8 From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.

  10. VEGF Mediated Angiogenesis From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.

  11. Angiogenesis Inhibitors • Angiogenesis inhibitors • Angiostatin • Endostatin • Protamine • Interferon • Use in treating cancer. From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.

  12. Angiogenesis Inhibitors From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.

  13. Invasion and Metastasis • Cancers spread through invasion and metastasis. • Invasion is the direct migration and penetration of cancer cells into tissues. • Metastasis refers to the ability of cancer cells to enter the vasculature and migrate to distant sites.

  14. Invasive Behavior of Cancer Cells • Changes in adhesive forces between cells. • Cell to cell adhesion proteins such as E-cadherin. • Cell motility • They produce signaling molecular that direct their movement. • Production of proteases • Plasminogen activator – converts plasminogen to the active proteas eplamin.

  15. Alterations in Cell Adhesion Molecules • Normal melanocytes express E-cadherin. • Melanoma cells express N-cadherin. • Low levels of E-cadherin allows detachment from keratinocytes. • High levels of N-cadherin allows interaction with stroma.

  16. Production of Proteases • Plasminogen Activator breaks down plasminogen to plasmin. • Most tissues have hight concentration of plasminogen. • Plasmin works by: • Degrading components of basal lamina and ECM • Cleaving inactive precursors of MMPs From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.

  17. Invasion and Metastasis

  18. Metastatic Potential of Cancer Cells • Experiment done to examine the metastatic potential of melanoma cells. • Heterogenous population of tumor cells – only some cells will form metastases. • Tumors are clonal by nature. Only certain cells have invasive characteristics. From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.

  19. Location of Metastases • Bloodstream carries cancer cells all over the body. • Each type of cancer preferentially metastasizes to particular locations. • This depends on: • Pattern of blood flow • Organ specific factors • Tumor Progression • Immune System From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.

  20. Location of Metastases • Organ Specific Factors • Some tissues secrete GFs that stimulate proliferation of cancer cells. • When prostrate cancer cells are cultured with bone, kidney or liver cells and injected into mice the cells incubated with bone cells form the most tumors. • Tumor Progression • Cancer cells change as they progress. • A metastatic tumor may be larger and more aggressive than the primary tumor due to acquired changes in the cells.

  21. Immune System and Metastasis From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.

  22. Tumor-Host Interactions From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.

  23. Metastasis and Research • Metastasis is a property that makes cancer so dangerous. • Scientific research is focused on identifying molecules that could block metastasis. • Metalloproteinsases • Metastasis promoting genes • Twist gene – regulates the activity of a specific group of genes during development (activates proteins that cause cells to lose adhesive properties, become motile and migrate). • Metastasis suppressor genes (cell adhesion molecules) • CAD 1 gene – encode for E-cadherin

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