Tumorgenesis Flashcards
What is the definition of hypertrophy?
Increase in cell SIZE in reaction to physiological or pathological stimulus
- Occurs in cells unable to divide
- Physiological examples: Skeletal muscle hypertrophy with training, increase in cell size in cardiac muscle
*REVERSIBLE → when the stimulus is gone, hypertrophy is reverted
What is the definition of hyperplasia?
Increase in the NUMBER of cell in response ot physiological or pathological stimulus
- Occurs in cells with a capacity to divide
- Physiological examples: Hyperplasia of epithelial cells in female breast during pregnancy, Liver regeneration
*REVERSIBLE → when the simulus is gone, hyperplasia is reverted (reversible even if happens from pathological stimulus)
What is the definition of neoplasia?
Neoplasm = new growth
Pathological disturbance of growth → excessive and unceasing proliferation of cells, indpendent of normal regulatory controls → IRREVERSIBLE
- Arises from genetic alterations → cells are not genotypically or phenotipically normal
- Neoplasms can be benign (not cancer) or malignant (cancer)
What is the definition of dysplasia?
Abnormal change in cell size, shape, organization
What defines a benign vs a malignant tumor?
Benign:
- Growth confined to a specific site, give no evidence of invading adjacent tissue
- Eptiehlial growth that has not penetrated throught the basement membrane —> NOT metastatic
- Mostly harmless
- Problems if they release high levels of hormones or in specific locations (brain)
Malignant:
- Aggressive growth that shows evidence of being locally INVASIVE
- Possibly metastatic
What are most (90%) of cancer-related deaths the result of?
They are the result of metastasis spawned from original primary tumours to bones, liver, brain, lungs, distant lymph-node, etc.
*Different cancers have preference metastasis spots
What are the characteristics of the tumour growth model?
- Most human cancers develop over many decades of time → age is a large factor in the incidence of cancer
ex: Lung cancer curve follows cigarette consumption curve, but with 10 years of delay
*Hypothetical, NOT actual → the population of cancer cells doubles at every division
What are important structure of the intestine for tumorgenisis?
*Well-documented in the epithelia of intestine (high rate of turnover)
Epithelia = site of most pathological changes associated with development of colon carcinomas
Basement membrane (basal lamina) = layer on which epithelia is anchored (separates capillaries from the epithelia)
What are the multiple steps of tumorgenesis for the metastatic colorectal cancer?
- Normal intestine epithelium → inactivation of APC TSG
- Dyplastic epithelium
- Early adenoma (benign) → activation of K-ras oncogene → intermediate adenoma (inactivation of TSG on 18q)
- Late adenoma → Inactivation of TP53 TSG = Bypass of senescence
- Carcinoma (malignant) → Inactivation of other tumor supressor genes
- Metastatic colorectal cancer (By-passed the basal membrane)
What is a carcinoma in situ?
- Not a benign neoplasm, its a carcinoma (stage 0, just before actual cancer)
Has biological genotype and phenotype of a malignancy, but:
- Not invaded throught he basement membrane
- Cannot metastasize in its current state
- Considered «pre-malignant» or «pre-cancerous»
- Patient will be cured if completely removed/treated
What is epithelial to mesenchymal transition (EMT)? (general definition)
Cellular process during which epithelial cells (by downregulation of their features) acquire mesenchymal phenotypes
Cells have fibroblast-like morphology + increased migratory capacity
Normal epithelial cells = formation of a barrier, highly organized
After EMT → less organized, more capacity to spread out
What do core EMT changes include?
- Cytoskeletal remodeling
- Cell-cell adhesion weakening
- Acquisition of cell motility
- Basement membrane invasion
*Change in gene expression pattern → genes associated with EMT are turned on
What are the steps of the invasion-metastasis cascade?
- Localized invasiveness enable in site carcinoma cells to breach the basement membrane
- Intravasation into lymphatic or blood vessel
- Blood vessels can transport cancer cells to distant sites
- Cancer cells colonize to form metastatic tumors
What is the importance of MET?
MET = mesenchymal to epithelial transition
Cells go through EMT to be able to metastasize, then MET to set camp elsewhere
Mesenchymal-like cells may:
- acquire apical-basal polarity
- reorganize their cytoskeleton
- exhibit increased cell-cell adhesion
Result = organized epithelium
