Lecture 4 2/7/25 Flashcards
What are the hallmarks of metastasis?
-dissociation of cells due to decreased E-cadherin
-invasion into the extracellular matrix via proteases
What are the steps of metastasis?
-cancer cells leave site of primary tumor
-cells pass through to tumor basement membrane and then through or between endothelial cells
-cells enter circulation
-cells resist anoikis (cell death due to loss of cellular contact)
-cells evade immune recognition
-cells arrest at distant organs
-cells leave circulation
-cells survive in a hostile microenvironment
What are the characteristics of metastatic inefficiency?
-metastasis is inefficient
-less than 1% of cancer cells that successfully enter circulation survive at distant sites
-metastatic cells must recognize, adapt, and endure the new environment to be successful
What is premetastatic niche?
-modulation of secondary microenvironment before cancer cells arrive
-early and effective interaction with stromal and inflammatory cells within new environment
-allows select populations of cells to survive and proliferate
How do neoplasms arise?
-arise from accumulation of mutations
-evade normal constraints of proliferation
-promote immortalization
-modify and maintain a supportive niche for survival and expansion
What are the characteristics of neoplasia in the early steps?
-DNA mutations allow for uncontrolled cell proliferation and tumor formation
-formerly normal cells undergo irreversible genetic changes
-cells become unresponsive to ordinary controls on cell growth
What are the characteristics of cellular mutations?
-each time a cell divides, it incurs mutations and/or errors with replication
-mutations can be inherited or environmental
-most mutations are silent and do not affect cell function
-mutations that disable tumor suppressor genes and/or activate proto-oncogenes are important for tumor formation
What are the characteristics of multi-stage carcinogenesis?
-results from accumulation of mutations in a stepwise fashion over time
-non-lethal genetic damage is key to carcinogenesis
-tumor is formed by clonal expansion of a single precursor cell that has incurred genetic damage
What are the steps of multi-stage carcinogenesis?
-initiation
-promotion
-progression
What are the characteristics of initiation?
-mutation of a single gene
-may provide survival advantage to the cell
-irreversible
What are the characteristics of promotion?
-proliferation of initiated cell in response to stimuli
-non-mutagenic
-reversible
-creates a proliferative environment for initiated cells
What are the characteristics of progression?
-tumor going from benign to malignant
-accumulation of mutations leads to uncontrolled cell growth
-irreversible
What are the intrinsic factors that allow tumors to arise?
-inherited errors
-mistakes in replication
-hormonal
-reactive oxygen intermediates
In which tumors does inflammation contribute to the formation of the tumor?
-squamous cell carcinoma in dogs with chronic keratitis
-feline injection site sarcomas
-feline post-traumatic ocular sarcoma
Which viruses can contribute to tumor formation?
-bovine leukosis virus
-avian leukosis virus
-feline leukemia virus
-bovine papillomavirus
Which extrinsic factors can lead to tumor formation?
-viruses
-chemical carcinogens
-radiation
What is a complete carcinogen?
carcinogen that, by itself, can push a cell through initiation, promotion, and progression
Which DNA mutations most commonly contribute to cancer?
-proto-oncogenes
-tumor suppressor genes
-DNA repair genes
-genes that regulate apoptosis
What are the characteristics of the G1/S checkpoint?
-monitors DNA integrity
-irreversibly commits cell resources to DNA replication
-cell replication occurs independent to extracellular growth signals after this checkpoint
What are the characteristics of the G2/M checkpoint?
-pre-mitotic checkpoint
-ensures that DNA replication is accurate before the cell divides
What is a proto-oncogene?
gene that promotes autonomous cell growth
What happens when proto-oncogenes are mutated?
-growth factors are overproduced
-growth factor receptors are always “on”
-cyclins that allow progression through the cell cycle are overproduced
How many copies of a proto-oncogene must mutate to cause cancer?
one copy
What are tumor suppressor genes?
genes that stop the cell cycle, such as p53 and BRCA-1
How many copies of a tumor suppressor gene must mutate to cause cancer?
two copies
What are the characteristics of familial cancer syndromes?
-mutated tumor suppressor gene is passed on to offspring
-only one additional mutation is required to inactivate the gene
-cancer occurs earlier in life
What happens when DNA repair genes are mutated?
the cell is able to accumulate more and more mutations without a way to fix them
What happens when genes that regulate apoptosis are mutated?
damaged cells continue to live instead of dying
