Project

Beurs Joke Tommelein: Radiotherapy-induced damage to cancer-associated fibroblasts promotes colorectal cancer progression through IGF-1/AKT signaling

Duration
01 October 2015 → 30 September 2016
Funding
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Laboratory medicine
    • Palliative care and end-of-life care
    • Regenerative medicine
    • Other basic sciences
    • Laboratory medicine
    • Palliative care and end-of-life care
    • Regenerative medicine
    • Other clinical sciences
    • Other health sciences
    • Nursing
    • Other paramedical sciences
    • Laboratory medicine
    • Palliative care and end-of-life care
    • Regenerative medicine
    • Other translational sciences
    • Other medical and health sciences
Keywords
cancer risk
 
Project description

  Each year, cancer of the rectum (or rectum) fixed at about 1500 Flemings. A large number of these patients is treated with chemoradiotherapy (irradiation in combination with chemotherapy) before the tumor is surgically removed. This treatment increases the life expectancy through improved local control. Patients with a fibrotic reaction, however, have a poorer chance of survival than patients with a fibro-inflammatory response. Fibrosis is composed of an increase in fibroblasts. A tumor be standing next to cancer cells also from cancer-associated fibroblasts, endothelial cells and various immune cells. This project studies how cancer-associated fibroblasts respond to radiotherapy and whether this response is associated with fibrosis and cancer cell survival mechanisms. Irradiation of cancer-associated fibroblasts with a therapeutic dose leads among other things to increased secretion of insulin-like growth factor 1 (IGF-1), a survival factor. The IGF-1 receptor and mediator of AKT survival are activated in irradiated cancer-associated fibroblasts, thereby increasing their aantat. It is important - in that colorectal cancer cells exhibit after treatment with the secretome of irradiated cancer-associated fibroblasts as well activation of the IGF-1 receptor and AKT. This results in more stretched cancer cells and stimulation of lactate exemption extracellular acidification, metabolic activity and growth. The same effects were obtained with recombinant IGF-1. Currently, experiments are conducted to evaluate the role of IGF-1 / IGF-1 receptor signaling in the survival effects of irradiated cancer-associated fibroblasts. Further research will show or radiotherapy, in combination with the blocking of IGF-1 / AKT signaling enhances the effectiveness of the cancer treatment, and reduce side-effects