Introduction to Cancer PDF

Introduction to Cancer Note-taker: Renad Reviewed by: Hawraa Alibrahim Black font meaning it doesn’t mention in class it’s mentioned in 221 recording Professor Amein Al-Ali Associate Professor , Department of Biochemistry College of Medicine, IAU Learning Objectives After participating successful...

Introduction to Cancer Note-taker: Renad Reviewed by: Hawraa Alibrahim Black font meaning it doesn’t mention in class it’s mentioned in 221 recording Professor Amein Al-Ali Associate Professor , Department of Biochemistry College of Medicine, IAU Learning Objectives After participating successfully in this session and related activities, students should be able to: • Understand the mechanisms by which unregulated cell growth may lead to cancer. https://youtu.be/GhfrHjBX5eA https://youtu.be/GhfrHjBX5eA Introduction to Cancer Lecture 1- Introduction to Cancer Lecture 2- What effect does cancer have on the patient? Lecture 3- Molecular Biology of Cancer I Lecture 4- Molecular Biology of Cancer II Lecture 5- Molecular Biology of Cancer III Introduction to Cancer What is Cancer? Normal cell • • • Normal cell growth- cells divide when new cells required Cell growth- slowly, tight control maintain cell tissue number. tight regulation of the cell cycle, DNA replication and cell division, enter cell cycle when instructed Cells stop dividing when need is met Cancer cell • • • Cancer- one cells changes Rapid uncontrolled growth Growing mass of cancer cells - tumour • Tumour formation- errors in signalling the end of cell division Introduction to Cancer • Cytokinesis Fig 11.2 Lewin et al. Introduction to Cancer • Entry Into Cell Cycle Is Tightly Regulated Cell divisions are not continuous ✓ controlled by: • External stimuli • Nutrient availability • • Extracellular signals Intracellular biochemical response: ✓ Cell Cycle Entry Or ✓ Arrest In A G1/G0 Phase ie: either growth promoting or inhibiting Introduction to Cancer Growth Factors Growth factors are usually secreted proteins or a steroid hormones {EGF (epidermal), NGF(nerve)} • • • Over 200 growth factors Circulate in the blood Required for Growth/differentiation • Cells do not divide or differentiate unless stimulated by environmental stimuli or growth factors Introduction to Cancer Growth Factors • Multiple effects • ✓ Regulation of cell cycle progression w • Effects on cell growth, differentiation and proliferation ✓ Cell survival ✓ Cell migration ✓ Cell death Balance of growth factors and their receptors ° ⑦ -- Introduction to Cancer Growth Factors • Growth factors regulate the cell cycle ✓ Normal and cancer cells cycle starts from quiescent non-dividing state, G0 ✓ stimulate progression through G1 • Growth factors regulate cell death ✓ Withdrawal of GF favours apoptosis ✓ Presence of GF inhibits apoptosis Introduction to Cancer Growth Factor Hormone Receptor Signals Gene transcription Proteins that inhibit intracellular signals Cell proliferation/cell death Introduction to Cancer Cell movement Types of Growth Factors: Use in Clinical Medicine • Single growth factors used in clinical practice ~ • Combination of growth factors- Proliferation of - cells ° - • O . 1 Examples of growth factors include – platelet derived growth factor (PDGF(platelet rich plasma) stimulate gene expression in monocytesmacrophages and fibroblasts-cell repair ), epidermal growth factor (EGF-nerves), erythropoietin (EPO-erythrocytes) -5 - GF - Introduction to Cancer PDGF EGF Epo • • • Types of Growth Factors: Use in Clinical Medicine Erythropoietin & GM-CSF EPO stimulates the proliferation of red cells and their differentiation EPO – used for the treatment of anemia of renal disease GM-CSF (Granulocyte-macrophage colony-stimulating factor) stimulates blood stem cell proliferation and mobilization (bone marrow transplantation and post chemotherapy to aid bone marrow recovery) Introduction to Cancer Growth Factors: Role in Cancer • Normal ✓ affect growth, proliferation and differentiation W ✓ not present all the time 2 3 : 2 . · • Cancers ✓ growth factors or their receptors overO active or active inappropriately ✓ Constitutive activation of receptors in cancer . 2 - : 2 - - - ↳ - - - Introduction to Cancer Growth Factors: Role in Cancer • • • Epidermal growth factor receptor II - breast cancer prognostic marker (over expression) Tumors produce growth factors such as IGF-1, IGF-2, EGF stimulate tumour growth in an autocrine fashion , effects the same cell that release it. (breast & prostate cancer) Mechanisms lead to growth factor over production in tumours is not clear Introduction to Cancer Mechanisms by Which a Normal Cell May Limit Proliferation Normal Cells • • • Maturation of cell into a Ot resting or quiescent state ° Post-mitotic differentiation - > Programmed cell death All of these processes are disrupted in cancer cells - - Introduction to Cancer Normal Cells May Exit From and Reenter the Cell Cycle • • Normal cells may respond to external signals -enter G0 Normal cells undergo limited number of divisions before they stop proliferating Introduction to Cancer Normal Cells May Exit From and ReEnter the Cell Cycle • • • Many cells slow down or halt cell proliferation as a person ages Quiescent cells may be stimulated to return to the cell cycle at G1 by environmental cues Cancer cells ignore signals to enter G0 and continue proliferating Introduction to Cancer Cell Differentiation Limits the Pool of Dividing Cells; Differentiation • • Normal cells-permanently leave cell cycle by differentiating into a specialized cell type Cells turning over rapidly constantly renewed from stem cells which proliferate and differentiate into more specialized cells e.g. skin, bone marrow, lining of intestine Introduction to Cancer Cell Differentiation Limits the Pool of Dividing Cells • • When a normal stem cell divides each daughter cell has a choice- it can remain a stem cell or go on a course leading to irreversible terminal differentiation Cells that have differentiated have reached their final specialized form Introduction to Cancer Cell Differentiation Limits the Pool of Dividing Cells Stem cells- essentially have unlimited capability to renew themselves • Inducing stem cells to enter post-mitotic differentiation- hence no capacity for proliferation • Tissue can decrease its pool of replicating cells • Cancer cells fail to undergo terminal differentiation and proliferate to form a tumour Introduction to Cancer Failure of Cells to Differentiate Can Lead to Tumour Formation Introduction to Cancer Cells are Subject to Growth Inhibition and May Exit From the Cell Cycle Some cells programmed to self-destruct by apoptosis • • Apoptosis eliminates healthy cells during development and eliminates damaged cells that can pose a threat to the organism Mutations that compromise a cell’s ability to carry out apoptosis can result in tumour formation Introduction to Cancer Figure 9.19 Purves et al., 7th ed Introduction to Cancer Figure 15.32 Karp 4th ed Introduction to Cancer Tumours are Masses of Cells Derived from a Single Cell • • • Cancers progress from: ✓ A single mutant cell ✓ To a tumour ✓ Then to metastasis Cancer is a multistep process that requires at least four to six different mutations to reach the tumour state Can take decades for a single mutant cell to proliferate into a palpable tumour Introduction to Cancer Tumours are Clonal • Single cell sustains mutation in one of its growthregulating genes- proliferates more rapidly • • Another cell of the clone acquires another mutation Tumor genesis progresses by clonal expansion, increasingly abnormal cells outgrow their less mutant neighbours Introduction to Cancer Figure 13.17 Lewin et al. Introduction to Cancer Cancer Cells Have a Number of Phenotypic Characteristics Cancer cells- several distinct properties Absence of Contact inhibition • do not stop dividing when they contact a neighboring cell (Contact inhibition) Introduction to Cancer • Growth properties of normal and cancerous cellscancer cells do not require attachment to a physical substrate in order to grow Figure 16.3 Karp 4th Edition Introduction to Cancer Normal cells Cancerous cells Figure 16.3 Karp 4th Edition Introduction to Cancer Cancer Cells Have a Number of Phenotypic Characteristics reduced requirement • Cancer cells have a greatly reduced requirement for growth factors to sustain proliferation resistant to growth-inhibitory • Cancer cells are resistant to growth-inhibitory signals Introduction to Cancer The Effects of Growth Factor Deprivation on Normal and Cancerous Cells Figure 16.4 Karp 4th Edition Introduction to Cancer Cancer Cells Have a Number of Phenotypic Characteristics Immortality • Unlike normal cells in culture, which halt division after a certain number of growth-and-division cycles: o Cancer cells are immortal o They do not stop dividing after a predetermined number of generations chromosomal aberrations • Cancer cells often have chromosomal aberrations, including changes in chromosome number and structure Introduction to Cancer Karyotype of a cell from a breast cancer cell line displaying a highly abnormal chromosome complement 1 2 4 3 5 1 6 7 8 13 14 15 19 9 10 16 21 20 11 17 12 18 22 X Fig 16.5 Karp 4th ed Introduction to Cancer Figure 13.27 Lewin et al. Introduction to Cancer Cancerous Cells are Distinguished From Normal Cells by a Number of Traits Figure 13.3 Lewin et al Introduction to Cancer Tissue Mass is a Balance Between Cell Division and Cell Death • In normal tissues, cells may proliferate continually but numbers remain steady because cell production is balanced by cell loss • If too many cells are produced, the rate of apoptosis will increase to dispose of the surplus • Deregulated cell growth is the defining feature of all cancers • Cancer cells fail to commit suicide when a normal cell would do so Introduction to Cancer Maintenance of tissue mass requires a critical balance between cell division and cell death Cell division (cell cycle progression – cell proliferation) Introduction to Cancer Apoptosis( cell death) Summary Introduction to Cancer Summary • • • Cell cycle is tightly regulated in normal cells Growth factors stimulate growth and differentiation of cells In many cancers, growth factors or their receptors are over active resulting in constant stimulation of cell growth Introduction to Cancer Summary • • • • Cancer cells do not respond to normal cell growth constraints and do not undergo terminal differentiation –Immortal Cancer cells have defects in their cell death machinery and do not undergo apoptosis- Favours Cell Division Tumours are derived from a single cell and are clonal Cancer cells are distinguished from normal cells by a number of phenotypic traits Introduction to Cancer Learning Objectives You should now be able to: • • • • • • Understand the mechanisms by which unregulated cell growth may lead to cancer. Appreciate that cells grow and divide at different rates and differentiate in response to stimuli by growth factors Understand that most cancers arise from a single cell and progress through several stages resulting in loss of cellular differentiation which may take several years Understand the concept of clonality, where cancer cells inherit the defects and phenotype of the mother cell Be able to describe phenotypic differences between normal and cancer cells Understand the concept of tissue mass being a result of balance between cell division and cell death Introduction to Cancer References • Molecular Biology of the Cell 4th ed Alberts et al. • Cell and Molecular Biology 4th ed Karp. • Cells Lewin et al. • Life 7th ed Purves et al. Introduction to Cancer