Cancer metastasis Clara Farque (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 channels Malignant cell = ability to invade basement membrane and metastasise

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

1) What is a matrix metalloproteinase. 2)Name three families of MMPs 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)

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)

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

What are the steps of metastasis? Black Exclaimed I’m Inside Potter After Escaping Azkaban Invade BM Passage through ECM Intravasation Immune interaction Platelet adhesion Adhesion to endothelium Extravasation Angiogenesis

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

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

Which are the 3 cancers with the highest mortality rates in women? Lung Breasts Bowel

Which are the 3 cancers with the highest mortality rates in men? Lung Prostate Bowel

What is the tumour staging system in breast cancer? TMN staging system. T = the size of the Tumour N = the Node involvement M = Metastases T1 = <2cm size T2 = 2 - 5 cm T3 = skin and/ or chest wall involved N0 = no axilliary nodes involved N1 = mobile nodes involved M0 = no metastases M1 = demonstrable metastases

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? Degree of tubule formation Extent of nuclear variation Number of mitosis Grades: 1 2 3

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%