cell communication and the non cellular stroma

Question 1

ECM

Answer 1

constitutes up to 60% of tumour mass in solid tumours

Question 2

what does ecm deposition result in

Answer 2

desmoplasia
- strongly linked to poor patient prognosis

Question 3

regulation of EMT

Answer 3

• activation of ‘master’ transcription factors
• downregulation of E-cadherin and epithelial genes
• upregulation of mesenchymal genes

Question 4

translocation of B-catenin in EMT

Answer 4

• cells at the tumour centre express B-catenin at the plasma membre
• cells at the invasive front express b-catenin in the nucleus
• nuclear B-catenin induces expression of EMT genes

Question 5

Src in EMT

Answer 5

• Src is a non receptor tyrosine kinase
• disrupts normal epithelial structure and promotes an invasive phenotype in cells
  -Src activity in colon and breast cancer correlates with tumour progression
• inhibition of Src reduces tumour cell invasion, delaying dissemination and progression of disease

Question 6

control of invasion by stromal cells

Answer 6

• in mouse model of intestinal carcinogenesis, colon adenoma cells recruit stromal cells
• a cap of bone marrow derived CD34+ myeloid cells is recruited to the invasive front
• the myeloid cells secrete MMP-2 and MMP-9 to enable collective invasion of the neoplastic cells into the mesenchymal layers of stroma

Question 7

fibroblasts in carcinogenesis

Answer 7

• a dynamic evolution of fibroblasts during tumour initiation and progression
• in the early stages of initiation, fibroblasts can drive proliferation of mutated cancer cells
• during cancer development, CAFs can then protect against tumour invasiveness
• in advanced stage disease, CAFs can be reprogrammed to allow tumour cell growth
• as the tumour evolves, CAFs reorganise the TME to promote angiogenesis and EMT