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Different names describing the same condition

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1. Cancer 2. Tumor 3. Neoplasm 4. Malignancy 5. Carcinogenesis

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Cells in the body undergo one of 3 processes

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1. Grow and divide 2. Differentiate (mature) or, 3. Die (apoptosis)

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Cell birth=

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mitosis

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Cell death=

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apoptosis

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Goal of the cellular society

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the survival of the entire organism, not of the individual cell

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Cellular social control

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made of cellular mechanisms and genes that control the birth and death of cells

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Growth factors

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are biological signals that either "turn on" or "turn off" cell growth

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Growth factors include

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1. Growth inducers 2. Growth suppressors

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Growth inducers

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substances that promote cell growth

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Growth suppressors

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signals that inhibit cell growth (turn off the division of cells)

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Cell differentiation (maturation)

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The process by which cells develop specialized organization, structure, and function of the tissue that they constitute by expressing specific genes.

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As a cell becomes more differentiated it loses

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its ability to replicate

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Cancer is a disease of

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1. Cell proliferation: Increased cell growth and division 2. cell differentiation: loss of differentiation

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Two major properties of cancer cells are

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1. Autonomy 2. Anaplasia

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Autonomy

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the cells independence from normal cellular controls which control cell growth and death

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Anaplasia

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the loss of differentiation

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Carcinogenesis

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multi-step process of tumor development

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Carcinogenesis includes

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1. Autonomy - loss of cells ability to control growth 2. Anaplasia- the loss of the cells ability to terminally differentiate 3. Metastasis- the cell has to travel to distant tissue and invade and colonize it

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1. Autonomy

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Cells that disobey the social control mechanisms of normal cells, proliferate to form tumors

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When a cell loses its ability to respond to social control signals (growth factors) it does not _______, rather it continues to divide without restraint

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differentiate

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The descendants of the cell that lose its ability to differentiate and continues to divide without restraint becomes founders of the

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Neoplasm (tumor)

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One mechanism that can trigger normal cells to divide is

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damage to tissues

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Growth factors in normal cells

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1. Help regulate cell population density 2. include inducers and inhibitors (suppressors) 3. Normal cells depend on other cells for growth inducers

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Growth factors in cancer cells are unbalanced and

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1. cells are chronically stimulated by growth inducers 2. cells do not respond to growth suppressors 3. cancer cells either need no growth inducers to divide, or produce their own (autocrine) growth factors

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Dividing cells are more prone to

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mutations

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Cancer is caused by mutations of the genes that regulate cell

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Proliferation and differentiation

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Three main genetic mechanisms have a role in the development of tumors

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1. Mutations resulting in hyperactivity of genes that stimulate growth 2. Mutations resulting in loss of activity of genes that inhibit growth (inactivated tumor suppressor genes) 3. Over-expression of genes that prevent apoptosis (normal cell death) allowing continued growth

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Mutated genes that stimulate growth

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Oncogenes

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How do oncogenes or inactivated tumor suppressor genes cause a tumor cell to proliferate indefinitely?

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One explanation, which is just one part of the answer, involves the enzyme telomerase which acts on the telomeres

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In immortal cancer cells, the enzyme telomerase

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adds nucleotides back to the telomere. With a full length telomere, cells continue to divide and do not die.

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Mutations that decrease communication between cells=

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increased cell growth

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Cancer cells display anchorage-independence

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they continue to divide without being anchored

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Dysplasia

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abnormal changes in size, shape, and organization of mature cells (atypical hyperplasia)

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1. Autonomy- Dysplasia (3 things)

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1. Local increase in cells due to rapid proliferation 2. Variation of cell shape and size: due to rapid mitosis 3. Loss of normal arrangement of cells: Disordered cells

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Neoplasia

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The stage when cancer cels invade and destroy neighboring tissue

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2. Anaplasia

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Differentiation

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Within a developing embryo, cells are?

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Less differentiated

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Undifferentiated cells in adults are known as

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Stem cells

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Cancerous cells are less differentiated and resemble

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embryonic cells

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In adults, two types of cells can develop into tumors

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1. Stem cells (undifferentiated) 2. Normal, differentiated cells

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Stem cells

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Are not terminally differentiated Can divide without limits

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Normal stem cell division

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Each division generates one daughter stem cells and one differentiated daughter cell

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To produce a growing tumor

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A stem cell fails to produce one non-stem cell daughter in each division. Thus, proliferating and causing imbalance in cell production versus cell destruction

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Normal, differentiated cells

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can develop into tumors by transformation

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Transformation

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the process by which a normal cell becomes a cancer cell

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Transformation is the process of

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Genetic mutation

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The mutated genes involve

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Growth factors

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The less the tumor resembles normal tissue

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the more undifferentiated (anaplastic) and malignant it is.

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In transformation, re-activation of proto-oncogenes can transform a well- differentiated cell to a

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less differentiated cell

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carcinogenic agents can mutate prot-oncogenes by

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re-activating them thus causing the cell to become less differentiated

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Cancer is considered to be a disorder of growth and differentiation because

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it resembles undifferentiated tissue

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Oncogenes

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Mutated genes that stimulate growth (proliferation)

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Proto-oncogenes

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genes that are normally turned off in a differentiated cell, but when reactivated , they transform a normal cell into a less differentiated cell (anaplasia)

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Metastasis

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The spread of tumor cells from the primary site of origin to a distant site

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The major cause of illness and death from cancer

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Metastasis

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Primary tumors are more easily eradicated by ______ than trying to control metastasis

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therapies

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Tumor spread depends on

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1. Rate of growth of the tumor 2. The degree of differentiation of the tumor 3. The presence or absence of anatomical barriers 4 Other biological factors (health and immune status)

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Tumor spread includes

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A. Local spread by direct invasion of contiguous organs B. Metastasis to distant sites (organs)

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Local spread (local invasion)

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is the first step in metastasis and a prerequisite of metastasis

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At first, local invasion occurs

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as a direct tumor extension

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In local invasion.. Eventually cells or clumps of cells detach from

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the primary tumor and invade the surrounding interstitial spaces

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The mechanism of local invasion include:

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1. Cellular multiplication 2. Decreased cell to cell adhesions 3. Release of lytic enzymes 4. Mechanical pressure 5. Increased motility of the individual tumor cells

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Cellular multiplication

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Depends on the rate of cell division and cell loss. It is related to autonomy

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Decreased cell to cell adhesions

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Cancer cells do not adhere to other cells like normal cells do. Thus, cancer cells slip between normal cells, resulting in invasion of distant tissues.

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Reasons for decreased adhesions

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a. Changes to cytoskeleton (protein filaments) b. Changes to fibronectin: defective, low levels, or loss of fibronectin

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Changes to the cytoskeleton

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cytoskeleton is composed of a network of protein filaments, which control the shape and internal organization of the cell. In cancer cells, the filaments are not well organized resulting in rounded appearance which slip between cells more easily.

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Firbonectin

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A glycoprotein preset on the cells plasma membrane and serves as an anchoring molecule to: 1. hold cells in place 2. Help to keep the cells internal organization 3. Hold receptor molecules in certain arrangements

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In cancer cells, fibronectin is decreased, defective, or broken down, causing changes in

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1. Cellular organization (decreased) 2. Cell-to-cell adhesion (decreased) 3. Cellular migration (decreased)

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Release of lytic enzymes

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Tumor cells release lytic enzymes that digest proteins and destroy normal tissue a. protease b. collagenase c. plasmin

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Protease

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destroy proteins in general

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Collagenase

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destroys collagen

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Plasmin

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destroys the basement membrane (extracellular mix)

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Mechanical Pressure

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Tumor cells make and secrete a protein named autocrine motility factor (AMF)

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AMF causes cancer cells to grow

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pseudopodia (fingerlike projections)

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Pseudopodia applies pressure that...

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forces them along the lines of least resistant of a tissue, similar to plants forcing roots into the soil

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Pressure from the growing mass could block local blood supply leading to..

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local tissue death and thus reducing the mechanical resistance of the normal tissue

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Increased motility

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The pseudopodia also enable cancer cells to move and allows them to migrate to other parts of the body

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_____ is integral to the entire process of metastasis

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Locomotion

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Metastasis to a distant site

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Three- step theory of tumor cell invasion of the extracellular matrix

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Three- step theory of tumor cell invasion

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1. Attachment 2. Dissolution 3. Locomotion

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1. Attachement

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surface receptors on the tumor cell bind to the basement membrane in the extracellular matrix

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2. Dissolution

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the extracellular matrix is degraded by lytic enzymes secreted by the tumor cell (proteases, plasmin)

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3. Locomotion

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the tumor cell migrates through the degraded basement membrane -pseudopodia of cancer cells cross the basement membrane enabling the cell to move in and out of blood and lymph vessels

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Metastasis involves a series of sequential steps

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1. Direct or continuous extension of local invasion of tumor cells into the surrounding tissue 2. Penetration 3. Release into: lymp & blood 4. transport to secondary site 5. Entry into the secondary site (metastasis)

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1. Direct or Continuous extension

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The earliest invasions is continuous extension. The tumor cells extend into the surrounding tissue as they grow, without breaking away from the primary mass Then the loss of adhesions allows the tumor cells to slip past one another

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2. Penetration

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Into either body cavities or capillaries

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Penetration into body cavities (implantation)

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cancer cells invade through serious membranes (peritoneum) and implant to become distant metastases in abdominal cavity

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Penetration into capillaries: lymph or blood

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Tumor cells spread to distant site by penetrating: Lymph capillaries or Blood capillaries Capillaries are thin-walled vessels so they do not offer mechanical resistance to penetration by tumor cells Clusters or single cells separate from the primary timor mass and disseminate though the lymph and blood

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Release into Lymph or blood

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the most common route for distant metastases is through the lymphatics because lymph capillaries are the easiest to penetrate (have the thinnest walls)

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Tumor cells enter lymphatic channels and are carried to

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the regional lymph nodes

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The first evidence of spread for many types of cancer is

answer

a mass in the regional lymph nodes

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When a cancer cell becomes lodged in a lymph node one of the following may occur

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1. Tumor cell death due to inflammatory reactions and macrophage activity in the node 2. Growth into a discernible lump 3. Sustained dormancy for unknown reasons 4. Detachment from the node and entrance into the larger lymph vessels

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Tumor spread through the lymphatic system eventually moves into

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the blood

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Tumor cells in lymph vessels form a

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moving mass (embolus)

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Embolus travels to the largest lymph vessel and from there is moves into

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venous bloos (subclavian veins) and enters the right atrium and ventricle

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The first organs capillary bed that the embolus goes to is in the

answer

lungs

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Growth of tumors depend on

answer

adequate blood supply

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angiogenesis

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formation of new blood vessels

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In order to spread to distant organs from the blood (emboli), tumor cells have to:

answer

1. Escape host defenses 2. Lodge in a capillary bed of the target organ

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Once in the capillary bed of the target organ, the tumor cells

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Exit the capillary by actively invading the blood vessels wall move into the interstitial space grow in the local tissue

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Patterns of metastasis are regulated by

answer

1. Blood flow and location of capillary beds 2. Organ tropism

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Functional Significance of Increased growth of cancer cells changes:

answer

1. Indefinite proliferation 2. Telomerase remains long 3. Lower requirement for growth factors 4. Decreased density-dependent inhibition of growth 6. Gap junction blockage 7. Anchorage independence

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Increased potential for metastasis

answer

1. Decreased cell to cell adhesion 2. Reduced fibronectin 3. Disorganized cytoskeleton 4. Increased plasminogen activator 5. Pseudopodia and autocrine motility factor

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Tumor cell markers

answer

substances that are either produced by cancer cells or as the body's response to cancer cells. Not all tumor cells produce markers

question

Tumor cell markers include

answer

1. Genes (or oncogenes) 2. Antigens 3. Antibodies 4. Enzymes 5. Elevated normal substances such as certain hormones (insulin, prolactin) or calcium

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Tumor cell markers can be found

answer

On plasma membrane of tumor In various body fluids such as blood, cerebrospinal fluid (CSF) and urine

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Both humeral and cell-mediated immunity are

answer

employed against cancer

question

Tumors are classified according to

answer

1. The degree of differentiation 2. Tissue of origin 3. Cell type 4. Whether benign or malignant

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Grade I

answer

Well differentiated (least malignant)

question

Grade II

answer

Moderately differentiated

question

Grade III

answer

Poorly differentiated

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Grade IV

answer

Very poorly differentiated (most malignant)

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Carcinoma in situ

answer

Pre-invasive epithelial tumors (of squamous or glandular cell origin) that have not broken through the basement membranes of the epithelium

question

Cell type classification

answer

Tumors are named according to the tissues from which they arise with the suffix "oma"

Patho Chapter 9- Biology of Cancer and Tumor Spread – Flashcards

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