Invasion and Metastasis

Question 1

Are mainly benign tumors responsible for cancer-related deaths?

Answer 1

No, benign tumors are only responsible for 10% of cancer-related deaths
90% is metastases from malignant tumors

Question 2

Why do cancer cells metastasis?

Answer 2

Because of the restrictions by the tumor environment

Too little available oxygen and/or nutriment (lack of vascularization)

Question 3

What are the 6 steps invasion-metastasis cascade?

Answer 3

1. Localized invasion
2. Intravasation
3. Arrest in microvessels of various organs
4. Extravasation
5. Formation of a micrometastasis
6. Colonization and formation of a macrometastasis

Question 4

What is the first event that takes place for a carcinoma to become invasive?

Answer 4

Mesenchymal–epithelial transition (MET) => regain epithelial properties and integrate into distant organs

Question 5

Do circulating tumor cells (CTCs) have a bigger risk of metastases than CTC clusters?

Answer 5

No, even though cell clusters made up less than 3% of total CTC ‘events’ in the blood, more than 50% of the metastases were derived from clusters

Question 6

What are the four pillars of metastatic niche functions?

Answer 6

1. Anchorage
2. Survival
3. Protection
4. Proliferation
   => Therapeutic opportunities

Question 7

What are the 3 types of epithelial-mesenchymal transitions (EMT) and what is their function?

Answer 7

1. Mesenchymal: from primitive epithelia to mesenchymal cells (developmental process of organogenesis)
2. Fibroblast: from secondary epithelial/endothelial to fibroblast (fibrosis)
3. Metastatic: from epithelial carcinoma to secondary tumor (metastasis formation in cancer)

Question 8

What are the 3 steps of epithelial-mesenchymal transition (EMT) type 3 (metastasis formation in cancer)?

Answer 8

1. Loss of adherens/tight junction components and loss of cell polarity
2. Breakdown of basement membrane, cytoskeletal remodeling and apical constriction
3. Stromal invasion/migration