TGF-β

Question 0

Role of TGF-beta in nervous system physiology:

Answer 0

Implicated in:

1. Nervous system formation.
2. Neurogenesis.
3. Neuronal migration.
4. Synapse formation.
5. Differentiation and proliferation.

Question 1

What is TGF-beta?

Answer 1

A Th1 cytokine with various functions, acting as crucial growth mediator in several organs and systems.

Question 2

Role of TGF-beta in LOW grade gliomas:

Answer 2

Inhibitor of tumor growth.

Question 3

Role of TGF-beta in HIGH grade tumors:

Answer 3

Triggers cell proliferation.

Question 4

Mechanism of tumor suppressing effects of TGF-beta:

Answer 4

By the SMAD signaling cascade which results in activation of p21, a widely recognized anti-tumor molecule.

Question 5

Mechanism of mitogenic role of TGF-beta:

Answer 5

It is able to activate Ras protein and induce the MAP kinase signaling leading to ERK activation.

Question 6

Mutations in which 2 molecules in HIGH grade gliomas shift the balanced expression of the 2 pathways toward MAPK, confirming the tumor promoting effect of this cytokine?

Answer 6

SMAD2, and SMAD4.

Question 7

Role of TGF-b1 and b2?

Answer 7

Are also able to affect the tumor angiogenesis by regulating VEGF and its receptor, thus controlling the formation of tumor vessels.

Question 8

Which cytokine greatly enhances the action of TGFb1/b2 with VEGF/VEGFR?

Answer 8

HIF, and also bFGF –> Indicating synergistic cooperation of TGF-beta with other major mediators.

Question 9

Mechanism of increased tumor invasion by TGFb1/b2:

Answer 9

1. Upregulation of α5β3 integrins.

2. Positive correlation with MMP-2+9 at the extracellular area of glial cells plasma membrane.

Question 10

TGF-beta and E-cadherin:

Answer 10

TGF-b1/b2 downregulates the production of the cell adhesion molecule E-cadherin, restraining the migratory effects of cancer modulators.

Question 11

TGF-beta and immune system regulation:

Answer 11

Aberrations in TGF-beta levels may cause severe abnormalities on immune system regulation.

Question 12

High TGF-beta levels secreted by gliomas have what effect upon the immune system?

Answer 12

Inactivate the immune cytotoxic response via downregulation of Natural Killer Group 2 member D (NKG2D) receptor in their surface.

Question 13

IL-1 synergy with TGF-beta?

Answer 13

Has also been indicated to induce the expression of Bim-1, LIF, and Notch-2 proteins.

Question 14

Bim-1, LIF, and Notch-2 proteins are correlated with what?

Answer 14

With increased expression of NESTIN, indicating an augmented self-renewal rate of glioma stem cells.

Question 15

3 other mediators of tumor invasiveness:

Answer 15

Increased expression of N-cadherin, SIP-1, and beta-integrin –> Worse prognosis.