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CANCER METASTASIS Clara Farque ([email protected] ) Alex Hammant ([email protected])

CANCER METASTASIS Clara Farque ([email protected])[email protected] Alex Hammant ([email protected])

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Page 1: CANCER METASTASIS Clara Farque (c.e.Farque@warwick.ac.uk)c.e.Farque@warwick.ac.uk Alex Hammant (A.R.Hammant@warwick.ac.uk)

CANCER METASTASISClara Farque ([email protected])

Alex Hammant ([email protected])

Page 2: CANCER METASTASIS Clara Farque (c.e.Farque@warwick.ac.uk)c.e.Farque@warwick.ac.uk Alex Hammant (A.R.Hammant@warwick.ac.uk)

WHAT IS INVASION?

• The ability of cells to break through normal barriers (e.g. basement membrane), and then spread. • Into surrounding tissue• In lymphatic/vascular channelsMalignant cell = ability to invade basement membrane and metastasise

Page 3: CANCER METASTASIS Clara Farque (c.e.Farque@warwick.ac.uk)c.e.Farque@warwick.ac.uk Alex Hammant (A.R.Hammant@warwick.ac.uk)

WHAT ARE CADHERINS AND INTEGRINS?

• Cadherins : glycoproteins between cells : maintain position and polarity

• Integrins : glycoproteins between cells and stroma : anchoring

• Malignant cells: reduced expression of integrins and cadherins : cells detach from each other and move

Page 4: CANCER METASTASIS Clara Farque (c.e.Farque@warwick.ac.uk)c.e.Farque@warwick.ac.uk Alex Hammant (A.R.Hammant@warwick.ac.uk)

1) WHAT IS A MATRIX METALLOPROTEINASE? 2)NAME THREE FAMILIES OF MMPS.

3) WHAT COUNTERACT MMPS?

1) Enzymes which degrade extracellular matrix

2)

• Collagenases : degrade Collagen I-III

• Gelatinases : Collagen IV and gelatin

• Stromelysins : Collagen IV and proteoglycans

3) Tissue Inhibitors of Metalloproteinases (TIMPS)

Page 5: CANCER METASTASIS Clara Farque (c.e.Farque@warwick.ac.uk)c.e.Farque@warwick.ac.uk Alex Hammant (A.R.Hammant@warwick.ac.uk)

WHAT IS METASTASIS? WHAT ARE THE FOUR ROUTES OF METASTASIS?

•Ability of malignant cells to invade into lymphatics, blood vessels and cavities, and spread to distant (non contiguous sites)

• Transcoelomic• Lymphatic• Blood stream• Surgical (post-transplant)

Page 6: CANCER METASTASIS Clara Farque (c.e.Farque@warwick.ac.uk)c.e.Farque@warwick.ac.uk Alex Hammant (A.R.Hammant@warwick.ac.uk)

WHAT ARE THE COMMON SITES OF METASTATIC SPREAD (LYMPHATIC,

VASCULAR, TRANSCOELOMIC)

•Lymphatic : local and distal lymph nodes

•Vascular spread : lung, liver, bone and brain

•Transcoelomic spread : Ovary, stomach, breast, lung

Page 7: CANCER METASTASIS Clara Farque (c.e.Farque@warwick.ac.uk)c.e.Farque@warwick.ac.uk Alex Hammant (A.R.Hammant@warwick.ac.uk)

WHAT ARE THE STEPS OF METASTASIS?

Invade BM Passage through ECM

Intravasation Immune interaction Platelet adhesion Adhesion to

endothelium Extravasation Angiogenesis

BlackExclaimedI’mInsidePotterAfterEscapingAzkaban

Page 8: CANCER METASTASIS Clara Farque (c.e.Farque@warwick.ac.uk)c.e.Farque@warwick.ac.uk Alex Hammant (A.R.Hammant@warwick.ac.uk)

NAME AS MANY HALLMARKS AS YOU CAN?

• What happens first:• Genome Instability• Deregulating cellular energetics

• How does it survive (and become ‘immortal’):• Self sustaining growth signals• Evade growth suppression• Limitless/endless replication• Avoid immune destruction• Resist cell death• Tumour promoting inflammation

• How does it thrive:• Invasion and metastasis• Angiogenesis

Page 9: CANCER METASTASIS Clara Farque (c.e.Farque@warwick.ac.uk)c.e.Farque@warwick.ac.uk Alex Hammant (A.R.Hammant@warwick.ac.uk)

WHAT IS THE DIFFERENCE BETWEEN PRIMARY AND SECONDARY METASTASIS?

• Primary – site where the malignant neoplasm arises

• Secondary – metastasis e.g. carcinoma that has spread to another organ

Page 10: CANCER METASTASIS Clara Farque (c.e.Farque@warwick.ac.uk)c.e.Farque@warwick.ac.uk Alex Hammant (A.R.Hammant@warwick.ac.uk)

WHICH ARE THE 3 CANCERS WITH THE HIGHEST MORTALITY RATES IN WOMEN?

1. Lung

2. Breasts

3. Bowel

Page 11: CANCER METASTASIS Clara Farque (c.e.Farque@warwick.ac.uk)c.e.Farque@warwick.ac.uk Alex Hammant (A.R.Hammant@warwick.ac.uk)

WHICH ARE THE 3 CANCERS WITH THE HIGHEST MORTALITY RATES IN MEN?

1. Lung

2. Prostate

3. Bowel

Page 12: CANCER METASTASIS Clara Farque (c.e.Farque@warwick.ac.uk)c.e.Farque@warwick.ac.uk Alex Hammant (A.R.Hammant@warwick.ac.uk)

What is the tumour staging system in breast cancer?

TMN staging system.T = the size of the TumourN = the Node involvementM = Metastases

T1 = <2cm size T2 = 2 - 5 cm T3 = skin and/ or chest wall involvedN0 = no axilliary nodes involvedN1 = mobile nodes involvedM0 = no metastasesM1 = demonstrable metastases

Page 13: CANCER METASTASIS Clara Farque (c.e.Farque@warwick.ac.uk)c.e.Farque@warwick.ac.uk Alex Hammant (A.R.Hammant@warwick.ac.uk)

What is tumour grading?The grading is the degree of cellular differentiation based on histological appearance of the tumour.

e.g for breast cancer what are you looking for?

1. Degree of tubule formation2. Extent of nuclear variation3. Number of mitosis

Grades:

1 2 3

Page 14: CANCER METASTASIS Clara Farque (c.e.Farque@warwick.ac.uk)c.e.Farque@warwick.ac.uk Alex Hammant (A.R.Hammant@warwick.ac.uk)

WHAT IS THE NAME OF THE PROGNOSTIC INDEX IN BREAST CANCER?

• Nottingham prognostic index:

• Size x 0.2

• Stage (1 – 3)

• Grade (1 – 3)Score 5-year survival

>/=2.0 to </=2.4 93%

>2.4 to </=3.4 85%

>3.4 to </=5.4 70%

>5.4 50%