Tumour Angiogenesis, Invasion & Metastasis Flashcards
Describe the growth of malignant tumours
Malignant tumours = Unlimited growth as long as an adequate blood supply is available
(Benign tumours = self-limited growth)
Malignant tumour invasion
Tumour cells migrate into the surrounding stroma and spread through vascular/lymphatics to distant organs
What is metastasis?
Metastasis = Tumour cells spread from the primary site to form secondary tumours at other sites
What is involved in cancer metastasis?
Cancer metastasis - sequential, interlinked, selective steps (+ some stochastic elements)
Describe the influence of each metastatic cascade step in cancer
Each step is potentially rate limiting; failure of tumor cell to complete any step impedes that part of the process
Outline the key steps of cancer progression
- Transformation: Extensive mutagenic and epigenetic changes followed by clonal selection
- Angiogenesis - overcomes the limitations caused by hypoxia
- Motility + Invasion: Epithelial -> mesenchymal transition (invasive properties allowing intravasation + extravasation)
- Metastasis: Colonisation of target organs (expand from micrometastases)
What is angiogenesis?
Angiogenesis = formation of new blood vessels from pre-existing vessels
What is vasculogenesis?
Vasculogenesis is the formation of new blood vessels from progenitors
What is the role of developmental vasculogenesis?
developmental vasculogenesis = organ growth
What is the function of normal angiogenesis?
Normal angiogenesis:
- Wound repair
- Ovarian cycle(egg release)
- Placenta during pregnancy
What is the consequence of tumour angiogenesis (pathological angiogenesis)?
tumour angiogenesis = ocular and inflammatory disorders
How long can tumours survive without a blood supply?
Tumours won’t grow >1-2mm3 without their own blood supply before they become hypoxic
Tumours become hypoxic at 1-2mm3
Describe a tumour in situ (benign)
Cancers in situ remain differentiated
Describe the structure of an invasive cancer
Invasive cancers:
- lose their rigid structure
- ↑ blood vessel density within the tumour
Outline the stimulus of tumour angiogenic factor release
- Small tumour (<1-2mm^3) is self-sustaining
- Tumour become hypoxic - As it grows, inner tumour cells ↑ distance from nearest capillary
- Angiogenic switch occurs - stimulates production of vascular growth factors (e.g. VEGF)
- VEGF(cytokine) diffuses out to initiate endothelial cell proliferation (in nearby capillaries) = forms vessels around the tumour
Describe the role of hypoxia in tumour angiogenesis
Hypoxia is a strong stimulus for tumour angiogenesis
What is hypoxia?
Hypoxia = Insufficient oxygen is delivered to tissues.
↑ distance of tissue from capillary = hypoxia.
Hypoxia is a strong stimulus for tumour angiogenesis.
-Low oxygen tension <1% O2
What is the consequence of hypoxia in tumour tissue?
Hypoxia in tumour tissue - Activates gene transcription for proteins involved in angiogenesis, tumour cell migration and metastasis