Session 10 - NeoplasiaII Flashcards
Define invasion of malignant cells
The ability of cells to break through the basement membrane and spread
Where do malignant tumours invade?
Surrounding tissue, lymphatic and vascular channels
What are the steps of malignant cells invasion?
1) Grow and invade at primary site
2) Enter a transport system
3) Grow at the secondary site to form a new tumour
What is metastasis?
Spread of a malignant tumour to a distant non- adjacent site
What do malignant cells need to avoid in order to succesfully metastasise?
The bodies immune system
Shearing force of movement through body
Free radical damage
What three important alterations are required for invasion of surrounding tissue by carcinomas?
Altered adhesion, stromal and basement membrane proteolysis and motility.
Also need to generate new blood supply.
Why are the alterations required for invasion called EMT?
Because carcinoma becomes more like mesenchymal cell, so it is an epithelial to mesenchymal transition (EMT)
Change in phenotype, eventually undergoes MET
How does altered cell adhesion occur in malignant cells? (2)
Cell-Cell interactions
Reduced expression of cadherins, which normally bind cells together.
Cell - Stroma interactions
Reduced expression of integrins in maligant cells allows for movement
How do malignant cells proteolyse extracellular matrix and stroma?
Metastatic cells synthesise and release Matrix Metalloproteinases. These allow metastatic cells to digest ECM and move to and break through basement membrane
What does
MMP1 digest?
MMP2/9 digest?
MMP1 - Type 1 collagen
MMP2 - Type IV collagen
How does altered motility occur in malignant cells?
Changes in actin cytoskeleton, via integrin signalling.
Why is tumour growth halted once it reaches 1-2mm3 in volume?
Growth is halted due to lack of nutrients/oxygen. This alters the tumours microenvironment, making it hypoxic.
What does tumour hypoxia cause?
Upregulation of pro-angiogenesis factors such as
Angiopoietin, VEGF
What do angiopoietin and VEGF cause the growth of?
Growth of new, thin wall blood vessels that allow growth of tumour. Also provides another opportunity to enter the bloodstream.
How do malignant cells travel to distant sites?
1) Blood vessels via capillaries and venules (tumour embolisis). No elastase so no arterial movement (CVS1!)
2) Lymphatic system
3) Fluid in body (pleura, peritnoeal, pericardial and brain ventricles), which is known as transcoelomic spread.
What must a cell does once it reaches a secondary site?
Extravasation (move out of a vessel) and growth
What is the consequence of failed secondary site invasion?
Micrometastases, which are harboured by many disease free people
How do neoplasmic relapses occur?
Due to micrometastases starting to grow
In which type of neoplasm is metastases via lymph nodes most common? What occurs?
Carcinoma
Local and distant lymph nodes affected, can often involve lymphatics of the lung
How does transcoleomic metastases spread?
To other areas in coleomic space or to adjacent organs
What is a cancer niche?
Interaction between malignant cells and nearby non-neoplastic cells, resulting in
In which type of neoplasm in metastases via blood most common? What are four common sites of blood borne spread?
Sarcomas
Lung, bone, liver and brain
What types of neoplasm often spread to lung?
Sarcomas (osteosarcoma)
Carcinomas (breast, stomach and large intestine)
Kidney (cannon ball secondary metastes)
Testis (malignant teratoma)
What types of of neoplasm often spread to liver?
Carcinomas of large intestine, via portal vein
Bronchial and breast carcinoma
What occurs in metastes to bone?
Can cause destruction of bone, leading to pathological fracture via carcinomas (bronchial, breast, thyroid and renal)
Can cause produce of dense bone via prostate cancer (osteosclerosis)
What occurs in metastases to brain?
Causes a wide range of neurological symptoms and act as a space occupuing lesion
What are metastasis to braince commonly from
Bronchial carcinoma Breast carcinoma Testicular carcinoma Testicular carcinoma Malignant melanoma
What is the bases of cancer staging?
The fact that metastasis is related to the size of the primary neoplasm
Give an example of a very agressive neoplasm
Small cell bronchial carcinoma
Give an example of a safer (relatively) carcinoma
Basal cell carcinoma of the skin
What are the two wasys in which the effects of a neoplasm on a host can be classified?
Due to direct local effects and indirect systemic effects
Give 3 local effects of benign neoplasms
Compression of adjacent structures
Blocking tubes and orifices
Ulceraton of surface mucosa
Space occupying lesion (brain)
Give 5 local effects of malignant neoplasms
Destroy surrounding tissue Infiltration around and into nerves, blood vessels and lymphatics Blocking tubes and orifices Ulceration of surface mucosa Space occupying lesion (brain)
What symptoms are caused by the systemic effects of neoplasm? Why?
Caused by cytokine release Reduced appetite and weight loss (cachexia) General discomfort (Malaise) Fever (pyrexia) Immunosupression Thrombosis
What are the four systemic systems which are affected by systemic effects of neoplasms?
Haematological
Endocrine
Skin
Neuromuscular
What are the systemic haematological repercussions of neoplasms and why do they occur?
Anaemia
- Due to malignant infiltration bone marrow
Low white cell and platelets
- Infiltration of bone marrow
- Consequence of treatments
Thrombosis
- Carcinoma of pancreas (secreted pro-clotting factors)
What are the two systemic endocrine repercussions of neoplasms?
Excessive secretion of hormones
- due to benign and malignant neoplasms of endocrine glands
Extopic hormone secretion
- ACTH by small cell carcinoma of bronchus
What are the four systemic skin repercussions of neoplasms?
Increased pigmentation
Pruritis (itching)
Fever
Dermatomyositis (inflammation of muscles and skin)
What are five neuromuscular issues associated with neoplasms
Problemas with balance Sensory/sensorimotor neuropathies Myopathy and mysathenia Dysfunction of white brain matter Not due to metastasis of braine
What is carcinomatosis?
Terminal cancer
What is embolic trauma?
Shearing force
Free radical damage
Immune attack
How do cancer cells grow new blood supplies?
angiopoietin and VEGF recruited from cancer niche
What is the seed and soil hypothesis of metastasis?
Once systemic circulation is bypassed, cancer may metastasise anywhere win the body with favourable interactions between malignant cells and local tumour environment (kidney notable in that cancers do not grow - incompatible niche)
Where are the most likely places cancer cells will grow?
Bone, lung, liver, brain
Which cancers most frequently spread to bone?
Breast, brain, liver, kidneys
??
What is size of tumour proportional to?
Likelihood of spread
What is paraneoplastic syndrome?
Effects of tumour burden, secreted hormone and other
What are the main effects of benign tumour?
Local and hormonal effects
What is erosion of epithelial surface called?
Ulceration
