20.1 The Development and Causes of Cancer Flashcards
any abnormal proliferation of cells
tumor
tumors that remain confined to original location; they do not invade surrounding normal tissue or spread to distant body sites
benign tumors
tumors that invade surrounding normal tissue and spread throughout the body via circulatory or lymphatic systems; the only tumors properly referred to as cancer
malignant tumors
most cancers are in 3 main groups:
- carcinomas
- sarcomas
- leukemias and lymphomas
malignancies of epithelial cells; comprise about 90% of human cancers
carcinomas
solid tumors of connective tissue (e.g. muscle, bone, cartilage, and fibrous tissue); rare in humans
sarcomas
arise from malignancies in blood-forming cells
leukemias
arise from malignancies in immune system cells
lymphomas
tumors develop from single cells that begin to proliferate abnormally; fundamental feature of cancer
tumor clonality
development of cancer is a multistep process; cells gradually become more malignant through a ()
progressive series of alterations
at the cellular level, development of cancer is a multistep process:
- mutation and selection for cells with progressively increasing capacity for proliferation
- survival of cancer cells
- invasion of cancer cells into neighboring tissue
- metastasis
mutation leads to abnormal proliferation of a single cells → grows into a population of clonal tumor cells
tumor initiation
additional mutations occur within cells of the tumor population
tumor progression
cancer cells are () → high frequency of mutations and chromosome abnormalities
genetically unstable
process of mutations conferring selective advantages to cancer cells (primarily rapid growth) → descendants of mutated tumor cells become dominant
clonal selection
clonal selection continues throughout tumor development → cells with () become more dominant
more mutations
studies of () provide a clear example of tumor progression during the development of a common human malignant tumor
colon carcinomas
overview of colon carcinoma development
- earliest stage of tumor development: increased proliferation of colon epithelial cells
- one of the cells in the proliferating population gives rise to a small benign neoplasm called an adenoma or polyp
- further rounds of clonal selection lead to growth of adenomas
- invasion of tumor cells into the underlying connective tissues indicates malignant carcinomas arising from benign polyps
- eventually, cancer cells penetrate the colon walls and metastasize to other abdominal organs, blood, and lymphatic vessels
characteristic properties of cancer cells that distinguish them from normal cells and contribute to malignancy:
- uncontrolled proliferation
- secretion of growth factors
- reduced cell adhesion molecules
- secretion of proteases
- promotion of angiogenesis
- abnormal differentiation
- failure to undergo apoptosis
- capacity for unlimited replication
in culture, normal cells display density-dependent inhibition, which allows them to
proliferate until they reach a finite cell density (partly determined by growth factor availability), after which they enter G0
normal fibroblast cells show contact inhibition, allowing them to ()
proliferate across a culture dish until they make contact with neighboring cells
ceasing of normal fibroblast proliferation upon cell-cell contact results in the formation of an ()
orderly array of cells on the dish
because cancer cells do not display density-dependent inhibition or contact inhibition, they ()
grow to high densities in culture and do so in disordered, multilayered patterns
cancer cells produce growth factors that stimulate their own proliferation: ()
autocrine growth stimulation
reduced growth factor dependence of cancer cells can also result from ()
abnormalities in intracellular signaling systems
most cancer cells are less adhesive than normal cells due to ()
reduced expression of cell surface adhesion molecules
loss of () is important in development of carcinomas
E-cadherin
why do cancer cells secrete proteases
proteases digest EC matrix components (e.g. collagen), allowing them to invade adjacent normal tissues
why do cancer cells promote angiogenesis
- new blood vessels deliver more oxygen and nutrients that contribute to tumor growth
- new capilliaries are also easily penetrated by tumor cells, contributing to metastasis
why do cancer cells promote abnormal differentiation
if cells are blocked at an early stage of differentiation, they can continually proliferate
growth of some tumors is driven by the proliferation of a () → produces more stem cells and differentiated tumor cells that lack the potential for continual self-renewal
subpopulation of cancer stem cells
DNA damage in cancer cells does not trigger apoptosis, allowing them to be ()
resistant to irradiation and chemotherapeutic drugs (act by damaging DNA)
cancer cells express high levels of (), allowing them to maintain chromosome ends for an indefinite number of divisions
telomerase
normal cells have limited amounts of telomerase and gradually lose telomeres → leads to ()
cessation of replication
conversion of normal cells to tumor cells
cell transformation
substances that cause cancer by acting to damage DNA and induce mutations
carcinogens
examples of carcinogens
- solar UV radiation
- aflatoxin
- benzo(alpha)pyrene, dimethylnitrosamine, nickel compounds (found in tobacco smoke)
other carcinogens are () that stimulate cell proliferation
tumor promoters
examples of tumor promoters
- asbestos
- Heliobacter pylori
- some viruses
how do tumor viruses directly cause cancer in humans or animals
they deliver genes that trigger tumor formation and progression (cancer)
fundamental abnormality of cancer: ()
continual unregulated proliferation of cancer cells
proliferation of cancer cells causes them to spread throughout the body and ()
interfere with function of normal tissues and organs
the loss of growth control exhibited by cancer cells is the net result of ()
accumulated abnormalities in multiple cell regulatory systems
4 most common cancers:
breast, lung, prostate, colon/rectum
