CSC Some Remembery Facts

Question 1

What might extrinsic cues do to functionally homogenous tumour cells?

Answer 1

Give them the potential to become heterogenous

Question 2

What determines the variability of CSCs

Answer 2

The experimental system

Question 3

What are CSCs influenced by?

Answer 3

Genetic aberrations of the tumour, stage of disease progression and types of drugs used to challenge the tumour

Question 4

In epithelial cancers what is the predictor of metastasis and death and what can trigger it?

Answer 4

An ESC-like transcription program that can be sufficiently mediated by c-Myc oncogene

Question 5

ESC-associated transregulators are more frequently over expressed in?

Answer 5

Poorly differentiated tumours.

Question 6

Poor prognosis tumours have lots of few CSCs?

Answer 6

Are like to have increased CSCs

Question 7

How does ZEB1 maintain stemness?

Answer 7

By blocking miR200 transcription (which inhibits stemness by targeting sox2 and klf4)

Question 8

What can be targetted to destroy CSCs?

Answer 8

EMT regulators (TGFβ) or real wnt miRNAs of ALDHs

Question 9

What might EMT accounts for in cancer?

Answer 9

Diversity and abundance of CSCs

Question 10

Induction of EMT in immortalised mammary epithelial cells lead to

Answer 10

Cells with stem like properties

Question 11

Cells on the leading edge of solid cancers (colon, breast & pancreas) are often?

Answer 11

Quasi-mesenchymal and express CSC markers

CD44, ALDH and CXCR1 in breast, CD133 and CXCR4 in pancreatic

Question 12

How can microenvironment trigger stemness/ csc phenotype

Answer 12

TGFβ influences zeb1 and twist, initiators of EMT and twist is a marker of undifferentiated mesenchymal cells.
Microenvironment - autocrine or paracrine signalling of EMT induces ie TGF or PDGF or IL6. Opposite at sites of metastasis MET to enable colonisation and a distant site

Question 13

what subtype of breast tumours resist conventional treatment and what markers do they express post treatment?

Answer 13

A subtype of breast cancers with TGFβ-like tumourigeneic gene pathways are expressed and characterised by mesenchymal markers which are expressed post treatment

Question 14

CSCs express what chemokine

Answer 14

CXCR4 which enable them to migrate along the gradient of ligand CXCL12 which originates from haematopoietic niches and other sites, facilitating metastasis

Question 15

What chemokine did CD133+ human pancreatic cancer express that enabled formation of metastasis after orthotopic xenografting? And what was this blocked by?

Answer 15

CXCR4+ and blocked by the CXCR4 inhibitor AMD3100

Question 16

Do cancer stem cells divide asymmetrically?

Answer 16

It has been claimed but has never been demonstrated in vivo and cannot be an obligate property because it would prevent numerical expansion of the CSCs

Question 17

What is the evidence of hierarchical organisation of CSCs?

Answer 17

CSCs are tumourigeneic cells that give rise to a hierarchy of tumourigeneic and non tumourigeneic progeny. Upon transplantation, tumourigeneic cells should give rise to more tumourigeneic cells as well as phenotypically distinct non tumourigeneic cells

Question 18

What is the evidence for phenotypic and functional heterogeneity of CSCs?

Answer 18

Flow cytometry distinguishes phenotypically distinct sub populations of cancer cells that are transplanted into test whether some are tumourigeneic whilst others are non tumourigeneic

Question 19

What has been used to block the self renewal pathway notch in breast cancer?

Answer 19

γ secretase inhibitors and chemo

Question 20

Why may some CSCs be radiation resistant?

Answer 20

Due to lower ROS levels and enhanced ROS defences compared to non tumourigeneic progeny