Cancer Flashcards
Cancer definition
A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph system
function of multicellular cells
It is to support the survival of the organism and the propagation of germ cells, which create more of the same organism
what dedifferentiates the cell
Mutations that lead to the conferring of a selective advantage of a cell over its neighbors, particularly with respect to increased growth and survivak, can impart a dedfifferentiated or selfish phenotype
Micro evolution of cancer
Initial mutations can be followed by successive rounds of mutations that lead to a micro-evolutionary process whereby an abnormal cell’s progeny rapidly undergoes natural selection through competition
this results in development of abnormal cells at expense of neighbors
Properties of cancer
-They exhibit uncontrolled proliferation
-They invade areas of the organism reserved for other cells
Benign cells
Cells that divide uncontrollably but do not become invasive
Malignant
Dividing cells with the ability to invade surrounding tissue and migrate to distal sites within the organism where they form secondary tumors or neoplasms
Metastais
Process of spread and invasion that results in death
Carcinomas
Epithelial cells (80% of all cancers)
Sarcomas
Connective tissue and muscle
Lukaemia and lymphoma
Blood cells and precursors
How to classify cancer cells
Have characterisitics that reflect their origin:
Melanoma makes melanin, hepatocarcinoma makes albumin
Molecular evidence that cancer originates from one cell
Philadelphia chromosome
X-Inactivation patterns
Philadelphia chromosome
-It causes chronic myelogenous leukemia
-Translocations of chromosome 22 to 9 results in truncated chromosome 22 ( Philadelphia chromosome)
-It also creates elongated chromosome 9
-This resutls in fusion oncoprotein BCR-ABL1
-ABL1 gene encodes for non-receptor tyrosine kinase
-This causes cell growth, survival, inhibition of apoptosis and activation of transcription factors
-results in constituitively expressed defective Abl
X-inactivation
Test for precancerous cells
Pap smear
Normal epigenetic function
-In normal cells: CpG island promoters are unmethylated and when active, as with tumor suppressor genes, are accompanied by histone marks such as acetylation and H3K4 methylation allowing transcription to occur on open chromatin structure
Epigenetic dysregulation
CpG islands for tumor suppressor gene promoters become methylated which forms silent chromain structure
Natural selection role in cancer
It favors proliferation and survival over genetic stability
Cell cycle and cancer
-Cells have checkpoints that halt cycle if DNA damage is detected and induce apoptosis if DNA repair is not possible
-Cancer cells aquire mutations to inactivate this process
Telomeres and cancer
-Cancer cells also escape the built in limit to cell proliferation that normal cells have via telomere shortening
-They express telomerase which repiars and elongates shortened telomeres
Tasks for metastasis
-the cell must break free from the ‘mother’ tumor and surrounding tissue that constrains movement; it must become invasive. This reuquires mechanisms to disrupt ECM and tissues
-The cell must travel to distal sites in the organism and survive, proliferate in new tissue environments. This requires entering the blood stream or lymphatic system trhough vessels and exit elsewhere
Enzyme that disrupts tissues and ECM
proteases
Micrometastasis
Formation of micro colonies or tumors at a new site
Angiogenesis
Bllod vessel formation
Angiogenesis formation
-Hypoxic conditions stimulate altered gene expression
-Transcriptions factors such as HIF1a are activated
-This results in expression of pro-angigenesis factors such as vascular endothelial growth factor (VEGF) which results in blood vessel formation
HIF1a
Hypoxic inducible factor
VEGF
Vascular endothelial growth factor
Metabolism of cancer
They switch from aerobic to anaerobic metabolism (glycolysis)
Tumor micro environment
Consists of fibroblasts, immune cells such as macrophages and endothelial (vascular) cells
-Tumor cells produce factors that recruit and modify stromal and immune cell behaviour to alter ECM of tumor environment
