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Flashcards in Invasion and Metastasis Deck (30):
1

Define invasion

Ability of cells to break through normal barriers e.g. basement membrane into the surrounding tissue

2

How to neoplastic cells invade and spread? 

Detachment of neoplastic cells from each other (through down-regulation of cadherin expression)

Attachment to ECM via specific receptors

Degradation of the ECM through secretion of collagenases and proteases

Locomotion through the ECM via secretion of motility factors

Cells then spread via vascular system, lymphatics or transcoelomic

3

How is cell adhesion altered?

Reduced expression and alteration of cadherins. Cadherins are Ca2+ dependent glycoproteins on the cell membrane that interact between cells and maintain cell polarity and structure. Reduction allows cells to  move apart

Reduced expression of intergins. Cell surefacec glycoproteins that anchor the cell to the basement membrane. Modifies contact between the malignance cell and stroma, allowing movement. 

4

How doe saltered enzyme synthesis promote metastasis?

Different enzymes can modify stroma allowing cells to break through the basement membrane and spread. e.g. MMPs, gelatinases, stromelysins

Malignant cells produce factors that stimulate stroma (fibroblasts) to synthesise more enzymes.

Remodelling determined by levels of MMPs and TIMPs (tissue inhibitor of MMPs). Can inhibit TIMP activity to alter balance of remodelling

5

What is metastasis?

Ability of malignant cells to invade lymphatics, blood vessels and cavities, and spread to distant sites. 

Cells must be able to invade from channels and grow at a distant site. 

6

What are the steps of metastasis?

Invade basement membrane

Pass through ECM

Intravasation

Immune interaction

Platelet adhesion

Adhesion to endothelium

Extravasation

Angiogenesis

7

Why don't all malignant cells metastasise?

Cells may invade and circulate but distal environment may not be appropriate for growth due to:

Incorrect receptors

Metabolic factors

Failure of angiogenesis

8

What is angiogenesis

Formation of small new vessels needed to maintain the growth of cells. 

Produced in response to growth factors.

9

Name 3 growth factors that promote angiogenesis

VEGF

Basic fibroblast growth factor

Angiopoietins

 

Anti angiogenic factors: thrombospondin, angiostatin, endostatin

10

Define primary and secondary metastasis

Primary: site where the malignant neoplasm arises

Secondary: carcioma that has spread to another organ

11

What are the routes of metastatic spread?

Lymphatics - spread via draining lymphatics to lymph nodes 

Vascular - spread by veins draining the lesion. GI tumours metastasise to the liver via portal vein. Cells that enter systemic veins form mets in the lung, BM, brain and adrenals. 

Transcoelomic - tumours in the abdomincal cavity or thorax can spread across coelomic spaces - peritoneal or pleural cavities. 

12

Common sites of vascular spread

Liver

Lung

Bone

Brain

13

Cancers which commonly spread to the lung via the blood

Sarcomas - osteosarcoma

Carcinomas - breast, stomach, large intestine

Kidney 

Testis

14

Cancers which commonly spread to the liver

GI carcinomas via portal vein

Bronchial carcinoma

Breast carcinoma

15

Cancers which commonly spread to the bone

Bronchial carcinoma

Breast carcinoma

Thyroid carcinoma

Renal carcinoma

All cause the destruction of bone 

16

Cancers which commonly spread to the brain

Bronchial carcinoma

Breast carcinoma

Testicular carcinoma

Malignant melanoma

17

Maligant neoplasms which spread via transcoelomic route

Ovary

Stomach

Breast 

Lung

18

What factors determine the effect a tumour has ?

Site

Extent of local spread

Sites of metastasis

Extent of metastatic spread

Functional effects

Paraneoplastic effects

19

What are paraneoplastic effects?

Effects which occur at distal sites due to the effects of tumour growth 

e.g. dermatomyositis. Cancer induces autoimmune response

20

Local effects of benign neoplasms

Compression - leading to pressure atrophy, or altered function

Partial or complete obstruction

Ulceration of surface mucosa

Space occupying lesion

21

Local effect of malignant neoplasm

Destroys surrounding tissue

Causes partial or complete obstruction 

Ulceration

Infiltration into nerves, blood vessels and lymphatics

Space occupying lesion

22

Name 5 systemic effects of neoplasms

Anaemia

Thrombosis

Myasthenia

Myopathy

Pigementation

Dermatomyositis

Cachexia

Malaise

Pyrexia

 

23

What are the haematological effects of neoplasms?

Haematological:
Anaemia - due to ulceration, infiltration of BM or haemolysis

Low WCC and platelets - due to infiltration of BM, chemotherapy

Thrombosis - cancers are pro-thrombotic

 

24

What are the endocrine effects of neoplasms?

Excessive secretion of hormones


Ectopic hormone production

25

What are the effects of neoplasms on the skin?


Pigementation
Pruritis
Dermatomyositis

 

26

What are the neuromuscular effects of neoplasms?

Neuromuscular:


Problems with balance


Sensory neupathy


Myopathy and myasthenia

27

How does local invasion of neoplasms occur?

Secretion of collagenases and elastases by neoplastic cells facilitates growth into surrounding connective tissue, vessels and nerves

28

Describe the patterns and sites of metastasis

Not all tumours metastasise. Route of metastasis depends on the type of neoplasm. 

Carcinomas first metastasise via lymphatics to lymph nodes and only via the bloodstream later in the disease.

Sarcomas metastasise via the bloodstream early, usually to the lung

Cancers of prostate, lung, thyroid, kidney and breast tend to metastasise to the bone

 

29

Describe the role of angiogensis in metastasis


Tumours need an adequate blood supply to be able to grow.

A vascular network is required for the metastatic spread.

Tumour cells secrete pro-angiogenic factors (VEGF, FGF) which induce endothelial cell growth, migration and vessel formation.

Tumours also fail to produce anti-angiogenic factors, resulting in uncontrolled growth of vessels.

Vessels anastamose with blood supply

30

Systemic symptoms assocaited with neoplasms


weight loss

loss of appetite

fever

malaiese

anaemia

 

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