Biology of Cancer and
Tumor Spread
Chapter 9
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Cancer



Derived from Greek word for crab,
karkinoma
Malignant tumor
Tumor

Also referred to as a neoplasm—
new growth
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Benign vs. Malignant Tumors
Benign
Grow slowly
Malignant
Grow rapidly
Well-defined capsule
Not encapsulated
Not invasive
Invasive
Poorly differentiated (cells) Well differentiated (cells)
Low mitotic index
(replication)
Do not metastasize (can’t
spread far)
High mitotic index
(replication)
Can spread distantly
(metastasis)
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Classification and Nomenclature

Benign tumors

Named according to the tissues from which
they arise, and include the suffix “-oma”
• Lipoma (lipo is fat, this is benign tumor of fatty tissue)
• Glioma (glial cell benign tumor)
• Leiomyoma (leio, myo = smooth, muscle BT)
• Chondroma (chondro = cartilage BT)
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Classification and Nomenclature

Malignant tumors (sarcoma)

Named according to the tissues from which
they arise
• Malignant epithelial tumors are referred to as
carcinomas

Adenocarcinoma (carcinoma = epithelial) (adeno =
gland)
• Malignant connective tissue tumors are referred to as
sarcomas

Rhabdomyosarcomas (straited-muscle-malignant
tumor)
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Classification and Nomenclature



Cancers of lymphatic tissue are
lymphomas
Cancers of blood-forming cells are
leukemias
Carcinoma in situ (CIS) in situ = in 1 place

Preinvasive epithelial malignant tumors of
glandular or epithelial origin that have not
broken through the basement membrane or
invaded the surrounding stroma
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Classification and Nomenclature
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Cancer Cells

Transformation

Autonomy
• Cancer cell’s independence from normal cellular
controls

Anaplasia (no control growth)
• Pleomorphic (multiple shapes)
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Cancer Stem Cells

Stem cells self-renew


Cell divisions create new stem cells
Stem cells are pluripotent

Ability to differentiate into multiple different cell
types
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Cancer Stem Cells
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Tumor Markers

Tumor cell markers (biologic markers) are
substances produced by cancer cells or
that are found on plasma cell membranes,
in the blood, CSF, or urine

Hormones
 Enzymes
 Genes
 Antigens
 Antibodies
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Tumor Markers

Tumor markers are used to:

Screen and identify individuals at high risk for
cancer
 Diagnose specific types of tumors
 Observe clinical course of cancer
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Cancer-Causing Mutations


Cancer is predominantly a disease of
aging
Clonal proliferation or expansion


As a result of a mutation, a cell acquires
characteristics that allow it to have selective
advantage over its neighbors
• Increased growth rate or decreased apoptosis
Multiple mutations are required before
cancer can develop
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Types of Mutated Genes
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Secretion of growth factors (autocrine
stimulation)
Increased growth factor receptors
Signal from cell-surface receptor is
mutated in the “on” position
Mutation in the ras intracellular signaling
protein (fabrication of proteins is multipled
greatly)
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Types of Mutated Genes



Inactivation of Rb tumor suppressor
Activation of protein kinases that drive the
cell cycle
Mutation in the p53 gene
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Types of Mutated Genes
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Types of Mutated Genes
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Angiogenesis


Growth of new vessels
Advanced cancers can secrete angiogenic
factors (VEGF) (hormone released around
the malignant cells)
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Angiogenesis
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Hallmarks of Cancer
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Telomeres and Immortality



Body cells are not immortal and can only
divide a limited number of times
Telomeres are protective caps on each
chromosome and are held in place by
telomerase
Telomeres become smaller and smaller
with each cell division
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Telomeres and Immortality
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Oncogenes and
Tumor-Suppressor Genes

Oncogenes


Mutant genes that in their nonmutant state
direct protein synthesis and cellular growth
Tumor-suppressor genes

Encode proteins that in their normal state
negatively regulate proliferation
 Also referred to as anti-oncogenes
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Mutation of Normal Genes

Point mutations


Changes in one or a few nucleotide base pairs
Chromosome translocation

A piece on one chromosome is transferred to
another
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Mutation of Normal Genes

Chromosome amplification

Duplication of a small piece of chromosome
over and over
 Results in an increased expression of an
oncogene
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Mutation of Normal Genes
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Mutation of Normal Genes
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Mutation of Normal Genes

Mutation of tumor-suppressor genes


Loss of heterozygosity


Allows unregulated cellular growth
Both chromosome copies of a gene are
inactivated
Gene silencing

Whole regions of chromosomes are shut off
while the same regions in other cells remain
active
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Mutation of Normal Genes
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Mutation of Normal Genes

Caretaker genes


Encode for proteins that are involved in
repairing damaged DNA
Chromosome instability


Increased in malignant cells
Results in chromosome loss, loss of
heterozygosity, and chromosome amplification
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Genetics and Cancer-Prone
Families



Mutagen exposure
Genetic events, but NOT inherited
Mutations in tumor-suppressor genes
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Genetics and Cancer

Exposure to mutagens

If the mutation occurs in somatic cells, it is not
passed to progeny
 If the mutation occurs in germline cells, it can
be passed to future generations
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Viruses and Cancer

Implicated

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Hepatitis B and C viruses
Epstein-Barr virus (EBV)
Kaposi’s sarcoma herpesvirus (KSHV)
Human papillomavirus (HPV)
Human T cell leukemia–lymphoma virus
(HTLV)
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Bacterial Cause of Cancer

Helicobacter pylori

Chronic infections are associated with:
• Peptic ulcer disease
• Stomach carcinoma
• Mucosa-associated lymphoid tissue lymphomas
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Inflammation and Cancer

Chronic inflammation is the most important
factor in the development of cancer

Cytokine release from inflammatory cells
 Free radicals
 Mutation promotion
 Decreased response to DNA damage
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Tumor Spread

Direct invasion of contiguous organs


Metastases to distant organs


Known as local spread
Lymphatics and blood
Metastases by way of implantation
(squeezing between planes)
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Phases of Tumor Spread




Transformation
Growth
Local invasion
Distant metastasis
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Local Spread

Invasion

Cellular multiplication
• Mitotic rate vs. cellular death rate
 Mechanical pressure
 Release of lytic enzymes
 Decreased cell-to-cell adhesion
 Increased motility
• Intravasation (entrance of tumor cells into circulation)
• Extravasation (exit of tumor cells from circulation)
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Three-Step Theory of Invasion

Tumor cell attachment


Degradation or dissolution of the matrix


Fibronectin and laminin (glycoprotein, ECM)
Enzymes
Locomotion into the matrix

Invadopodia (pseudopodia) (feet to invade)
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Metastasis

Spread of cancer from a primary site of
origin to a distant site

Steps
• Direct or continuous extension
• Penetration into lymphatics, blood vessels, or body
cavities
• Transport into lymph or blood
• Transport to secondary sites
• Entry and growth in secondary sites
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Distant Metastases


Metastasis often occurs in the first capillary
bed encountered by circulating cells
Organ tropism

Preferential growth of cancerous cells in certain
organs
• Growth factors, chemokines, hormones, tissue-selective
homing receptors, and chemotactic factors
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