Cancer and stem cells

Question 1

What is an oncogene?

Answer 1

A gene capable of transforming a normal cell into a tumour cell

Question 2

What is a tumour suppressor gene?

Answer 2

A gene that restricts proliferation

Question 3

What is intra-tumour heterogeneity?

Answer 3

Different cell types with different properties within the same tumour

Question 4

What is inter-tumour heterogeneity?

Answer 4

The tumours of patients with the same type of cancer have differences

Question 5

What is the stochastic model for cancer? (2)

Answer 5

• All tumour cells are equipotent and some of them stochastically proliferate while other cells differentiate
• All cells should theoretically be susceptible to chemotherapy

Question 6

What is the cancer stem cell model (CSC) for cancer?

Answer 6

Only a small number of tumour cells have the ability for long-term self renewal and they give rise to progenitors with limited proliferative potential that eventually terminally differentiate

Question 7

What are the therapeutic implications of the CSC model? (2)

Answer 7

• The cancer stem cells (CSCs) have a slower cell cycle so they evade drugs that target highly proliferative cells
• The CSCs survive and the tumour regrows with heterogeneity

Question 8

What are the common features of cancer stem cells and normal stem cells? (4)

Answer 8

• Self renewal
• Differentiation
• Ability for functional reconstitution
• Regulated by the same signalling pathways (e.g. hyperactivation of WNT is linked to colon cancer)

Question 9

What are possible origins of cancer stem cells? (2)

Answer 9

• Somatic mutation causes reprogramming of a specialised cell to a cancer stem cell
• Oncogenic transformation of pre-existing stem cells into cancer stem cells

Question 10

What methods can be used to define a cell as carcinogenic? (2)

Answer 10

• In vitro: establishment of cell lines that can self-renew and differentiate
• In vivo: ability to give rise to cancer when transplanted into animals

Question 11

What are the markers for haematopoietic stem cells (HSCs)?

Answer 11

CD34+ CD38-

Question 12

What is the functional assay to define haematopoietic stem cells (HSCs)? (2)

Answer 12

• Irradiate a mouse to destroy haematopoietic system
• Transplant HSCs, system is restored

Question 13

What is the functional assay to define acute myeloid leukaemia (AML) stem cells? (2)

Answer 13

• Irradiate a mouse to destroy haematopoietic system
• Transplant AML stem cells, mouse develops leukaemia

Question 14

How do AML stem cells compare to HSCs? (2)

Answer 14

• Marked by the same cell surface markers (CD34+ CD38-)
• HSCs can differentiate into the entire haematopoietic system but AML stem cells mostly differentiate into myeloid cells

Question 15

Why are glioblastoma (GBM) tumours heterogeneous? (2)

Answer 15

• Neural stem cells differentiate into glia and neurons
• GBM stem cells are thought to resemble neural stem cells

Question 16

How do you capture GBM stem cells in vitro? (3)

Answer 16

• Plate cells on laminin in the presence of FGF2 and EGF (same conditions as for neural stem cells)
• Cells express undifferentiated markers
• Differentiation potential varies depending on the tumour

Question 17

What is a xenograft model?

Answer 17

Transplanting tumour cells into animals

Question 18

What are the main approaches to studying cancer? (3)

Answer 18

• Xenograft models
• Cancer cell lines
• Genetically modified animals

Question 19

What are the limitations in studying tumourigenesis? (2)

Answer 19

• Hard to capture the early transition from a normal cell to a tumourigenic cell
• Lack of mechanistic insight

Question 20

How can limitations in studying tumourigenesis be overcome? (3)

Answer 20

• Reprogram already cancerous cells into pluripotent cells
• Introduce oncogenic mutations into normal human embryonic stem cells
• Observe differentiation