Tumor Invasion and Metastasis

Question 1

Invasion

Answer 1

Dissect through organ or tissue where cancer is located

Question 2

Metastasis definition

Answer 2

Ability to separate from primary tumor mass and implant at a discontinuous site

Question 3

General info of metastasis

Answer 3

Most can readily metastasize
Larger and more rapidly growing=more likely metastasis
30% of newly diagnosed solid cancer patients present with metastases (exluding basal cell carcinoma of the skin)
Reduces possibility of a cure

Question 4

Exceptions of cancers and metastasis

Answer 4

Malignant glioma of CNS
Basal cell carcinoma of skin
Both invade but not malginant

Question 5

Pathways of spread

Answer 5

Seeding
Lymph
blood

Question 6

Seeding of body cavities

Answer 6

Malignant neoplasm invades through organ and then cells enter open spaces
Cancer cells implant on surface of membranes, organs, and tissues in space

Question 7

Lymphatic spread

Answer 7

Most common carcinoma route
Invade lymphatic vessels and dividie in nearest lymph node
Exit lymph node via efferent vessels and spread to more distant nodes
Pattern is usually predicatble

Question 8

Upper outer quandrate breast drainage

Answer 8

To axillary nodes

Question 9

Hematogenous spread

Answer 9

Most common for sarcoma
Most commonly in veins
Cells invade the vein and follow venous blood flow to lung and liver (predominantly)

Question 10

Why lungs and liver?

Answer 10

All venous flow drains into SVC and IVC, into right side of heart and into lungs
Portal vein receives blood from areas predisposed to cancer (colon, pancreas, esophagus, stomach)

Question 11

Invasion of ECM steps

Answer 11

Dissociation
Attachment to ECM ptoeins
Degradation of ECM
Migration

Question 12

DIssociation of tumor cells

Answer 12

Down regulation of E-cadherins on tumor membranes

Mutation in genes for catenins…these help give E-cadherin its functional ability

Question 13

Attachment of tumor cells to ECM proteins

Answer 13

Receptors (like integrins) on tumor cell membranes bind to basement membrane proteins (like laminin, fibronectin, and collagen)
Tumor cells may have more integrin receptors or may have different types of integrins
Degraded ECM proteins may generate novel binding sites that bind to receptors on tumor cells

Question 14

Degradation of ECM by proteolytic enzymes

Answer 14

Enzymes secreted by tumor cells or ECM (cathepsin D, urokinase plasminogen activator, MMP (digest collagens))
Digestion creates channels for tumor cells to migrate through
Cleavage products generated (Growth facotrs, angiogenesis, chemoattractants)

Question 15

SUccessful cancers

Answer 15

Manipulate and utilize the ECM components to their advantage

Question 16

Vascular dissemination

Answer 16

Tumor cells invade vessel wall via enzymes
Aggregate into small clumps of tumor cells and platelets
Tumor embolus flows downstream and adheres to endothelial membrane at distant site
Burrow through basement membrane
Now within tissue discontinuous
Tumor cells porliferate, develop vascular supply and evade host defenses

Question 17

Homing

Answer 17

Anatomic considerations
Heterogeneitfy of both cell adhesion molecules of tumor and ligands of endothelial cells
Speicifc chemokine receptors (CXCR4 and CCR7 in breast cancers)
Some places are unpermissive (skeletal muslce)