Invasion and Metastasis Flashcards
What is invasiveness?
ability to thrust aside adjacent tissues, actively invade and destroy these tissues
What is metastasis?
the capability to leave a primary tumour, travel via the circulation to a distant tissue site and form a secondary tumour
What are the Five steps of metastasis?
1) Invasion and migration – tumour invades tissue and then migrates
2) Intravasation – when they go into blood stream by enzymes to break down the barrier to enter blood vessels
3) Circulation – circulate in blood stream
4) Extravasation – gets stuck in liver??
5) colonization, proliferation and angiogenesis
What is involved in stage 1 (invasion and migration) of metastasis
Cancer cells invade adjacent tissue
- Several lytic enzymes are secreted to degrade
extracellular matrix and facilitate migration
What is involved in stage 2 (intravasion) of metastasis
- Attach on the endothelial cells via adhesion molecules
- Secrete proteolytic enzymes enabling them to infiltrate the blood vessel
What is involved in stage 3 (circulation) of metastasis
travel via the blood stream (difficult for cancer cells)
- can select resistant and aggressive cancer cells which survive the blood stream
What is involved in stage 4 (Extravasation) of metastasis
- cells get stuck in the capillaries of organ(s)
- leave the blood stream by penetrating the endothelium through the proteolytic enzymes (break down)
What is involved in stage 5 (Colonization, proliferation and angiogenesis) of metastasis
- The cancer cells settle at distant tissue site(s) and builds
secondary tumour(s) - Then proliferates and induce neoangiogenesis (vessel formation) to ensure vascularization so they have nutrients at the secondary site.
What is grastrulation?
- Gastrulation is a phase early in the embryonic development, during which the single-layered blastula is reorganized into 3 germ layers: ectoderm, mesoderm and endoderm
- Ectoderm is the outer layer and can change their phenotype during gastrulation
- It can shed their epithelial character, adopt a mesenchymal type of cell character phenotype and establish the mesoderm
What is Epithelial to mesenchymal-like phenotype (EMT)?
EMT is a critical step in the development of invasive cancer cells
• It is a biologic process that allows a polarized epithelial cell to undergo multiple biochemical changes to assume a mesenchymal cell phenotype: Enables tumour to:
- enhanced migratory capacity
- invasiveness
- elevated resistance to apoptosis (resist death)
- increased production of extracellular matrix and enzymes that break down the barrier
When undergo EMT, become more invasive and deposits into secondary site.The epithelial–mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells; these are multipotent stromal cells that can differentiate into a variety of cell types.
What is Mesenchymal-epithelial transition (MET) (REVERSE – back to original character?
- EMT which takes place at the beginning of the invasion, is reversed during colonization
- This is called mesenchymal-epithelial transition (MET), enabling the cells to adopt the original epithelial character
Similar to primary tumour
Primary tumour has surrounding cells that undergo EMT, then invade and go into vessels and deposit into secondary sites and then MET (transition into new sites).
MET is believed to participate in the establishment and stabilization of distant metastases by allowing cancerous cells to regain epithelial properties and integrate into distant organs.
What are the factors of metastasis?
Various genetic, anatomic and physiological conditions affect metastasis, known as ‘metastasis factors’:
- Extracellular matrix (ECM), integrins, cadherins
- cell-cell adhesion molecules (CAMs)
- cellular movement (motility and chemotaxis)
- metastasis genes and suppressors
- proteinases (plasminogen activators, matrix metalloproteinases and their inhibitors etc) (breakdown the barrier to allow cancer to migrate)
- nature and location of primary tumours
- angiogenesis factors and immune system (need nutrients) (immune system can reject cancer cells but if immunocompromised, cancer cell can invade and form).
How do we assess the risk of regional and distant metastasis clinically?
Using clinical pathological information such as:
- Size and grade of tumour: how long has tumour been there or how has it grown (time)
- Lymph node status and extracapsular spread: see if tumour has spread to lymph nodes
- Lymphovascular invasion (if has invaded the vessels)
- Resection margin etc (taken out completely)
- Breast cancer – ER/PR status and HER2
- Age (e.g. some young breast cancer patients with triple negative breast cancer can have very aggressive cancers due to being a BRCA carrier and also a reason to develop cancer early). – may need to be more aggressive with treatment
How do we treat cancer patients and prevent future recurrence or metastasis?
Surgery: if cancer can be removed – this is the best treatment (e.g. breast cancer can just remove the breast.)
• Radiotherapy – can be used as a primary treatment to cure cancer but most of the time on its own its not effective
• Chemotherapy – only cures small cancers like lymphomas and testicular cancer – given as adjuvant treatment – given as prevention or conjunction with radiotherapy.
• Biology therapy like EGFR and HER2 inhibitors or hormone treatment (tamoxifen) in breast cancer
• Therapies against those genes/proteins that are involved in invasion
and metastasis – important in understanding biology
• Treatment intent:
- Primary, curative (radical) treatment: usually cancer has only localized to one site
- Adjuvant treatment – given as a prevention (radiotherapy, chemo, biological treatment or combination)
- Palliative treatment when incurable or metastasis (just to control the cancer and prolong the life by a bit)
What is Circulating tumour cells (CTCs)?
Intact tumour cells that have been shed into the blood stream from a primary cancer and it is thought to play a role in inducing metastasis in distant organs
- Rarely found in health individuals or patients with non-malignant diseases
