Oncology 6 Flashcards
What are some of the ways metastases can occur?
- bloodstream (hematogenous or vascular)
- lymphatics
- direct extension into neighboring tissues
- resection of tumors without clear margins
- benign mechanical transport
What is a skip metastasis?
- bypass local lymph
- form distant nodal metastases
Direct extension into neighboring tissues: How does metastasis occur with local invasion?
- local invasion and tumor angiogenesis
- venous drainage and further spread via metastatic cascade
- skip metastasis
Patterns of these determine common metastatic patterns
- regional venous drainage
- blood flow
- lymphatics
How does breast cancer metastasize?
spreads via lymphatics and vertebral venous system to bones in:
- shoulder
- hip
- ribs
- vertebrae
- lungs
- liver
How might resection of tumors without clear margins encourage metastasis?
new blood vessels form during healing process
Why does something like breast massage (benign mechanical transport) cause metastasis?
- assisted sentinel lymph node (SLN) localization
- can cause a cell to get loose and metastasize
What steps are required for metastasis of cancer cells?
- Spread of tumor within the tissue of origin through local invasion
- spread into micro-vasculature by intravasation
- circulate through vasculature before being trapped in the microvasculature of other organs
What is it called when tumor cells exit the blood vessel to other organs and form a secondary tumor? (not metastasis)
extravasation
Boundaries: Every normal tissue has boundaries. How do benign tumors act with boundaries?
- don’t cross them
- press against only
Boundaries: How do malignant tumors behave?
They have boundary issues. Spread and invade healthy tissue
What must a metastasizing cell do in new environment?
Must have adaptation of its cellular membrane proteins
Why does differentiation impact metastasis?
If it’s poorly differentiated, it can easily adapt in another location of the body
What is selective metastasis?
Metastasis occurs in some tissues but not others in certain cancers
What is explanation for selective metastasis?
Certain cellular environments are conducive to particular tumor growth and others aren’t.
How does a cancer cell change to adapt?
- Uses intercellular signaling
- Changes from one configuration to another in different environments
What is the Hayflick limit?
Aside from being programmed to die, all cells have a limit to how many times they can divide before they can’t divide anymore
Normal human fetal cells in a cell culture divide this many times
between 40-60x
Once cells reach their limits of division, they enter this phase
Enter a senescence phase and stop
Cell reproduction decreases with
physical age
Each mitosis causes shortening of these
telomeres on the DNA
Telomeres and aging
- telomere shortening makes cell division impossible
- correlates with aging
Cancer cells: immortal division
Have unlimited dividing potential
- they never stop
- they are true immortal cells
What is a telomere?
- region of repetitive DNA sequences at the end of a chromosome
- disposable buffers blocking chromosome ends
Telomeres are consumed during
cell division
What would happen without telomeres?
cells would lose the ends of their chromosomes during division and the info they contain
Telomeres protect the ends of the chromosome from:
- deterioration
- fusion with neighboring chromosomes
What replenishes telomeres?
TERT (telomerase reverse transcriptase)
Why is TERT important in normal cells?
needed to extend lifespans of certain cells (i.e. fetal stem cells)
TERT activation and cancer
TERT activation observed in more than 90% of all human tumors
TERT is part of the reason for this (hallmark)
limitless reproductive potential
What are the two main points that contribute to unlimited reproductive potential?
- loss of cell cycle checkpoints
- TERT
