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    Angiogenesis in Cancer

    Solid tumours initiate angiogenesis to support their growth by producing growth factors such as VEGF. Depriving the tumour of the excessive vessels that support its growth became the target for developing anti-angiogenic agents that could provide, in combination with chemotherapy, improved anti-cancer treatment. We have recently reviewed the literature in this area (Anti-angiogenesis in cancer therapy: Hercules and hydra).

    Mutations of PI3KCA have been reported in 10–20% of colorectal cancer (CRC), about 80% of mutations are found in two hot spots in exon 9 and exon 20 (reviewed in Cathomas 2014, see Figure below).

    We have chosen a model system in which to investigate regulators of angiogenesis secreted by colon cancer cells harbouring activating mutations of PI3K at each of these loci (Mutant PIK3CA promotes cell growth and invasion of human cancer cells). We used the DLD1 colon cancer cell line which contains the E545 mutation in the helical domain of exon 9 and the HCT116 cell line which has an H1047R alteration in exon 20 (kinase domain). Both both cell lines were genome edited in the lab of Bert Vogelstein generating cell lines harboring either the wild type (WT) or the mutated (MUT) allele. This system has the advantage that one can investigate the mutation of interest in an isogenic background.

    Our approach is:

    • Carry out microarray analysis of WT (harbouring only the WT PI3K) and MUT (harbouring only the mutated PI3K) DLD1 and HCT116 cell lines
    • Investigate the role of differentially regulated transcripts on primary endothelial cells  (by adding the purified protein, or co-culture with the CRCs) and CRCs (by genome editing the cancer cells to delete or over-express the gene of interest) in vitro using the following assays:
       
          o    Proliferation*
          o    Migration*
          o    Invasion*
          o    Matrigel angiogenesis assay
          o    Endothelial cell sprouting assay
      (*these experiments were carried out using the IncuCyte live-cell analysis system)

    • Dissect the molecular mechanism involved using gain of function and loss of function experiments
    • Test the role of the angiogenesis regulators in tumour development and metastasis in vivo by genome editing CRCs using CRISPR
    Read more...

    Additional Info

    • Programme Hellenic Ministry of Finance and Development & Tourism; Type of Grant: PA 2014-2020/Interreg Greece-Italy/2
    • Title Integrated Envirinomental Management (2.1); Title: Promoting Silver tourism through valorization of MED-diet and wellbeing routes in the CBC area; Acronym: Silver wellbeing
    • Funding Source Hellenic Ministry of Finance and Development & Tourism; Type of Grant: PA 2014-2020/Interreg Greece-Italy/2
    • Contract Number 5003627
    • Budget (for the team): Budget: 891.999,12 €. Principal Investigator for IMBB-BR: Theodore FOTSIS; Budget for IMBB-BR: 158.619,25 €
    • Duration 2018-2021

    Additional Info

    • Programme Competitiveness, Entepreneurship & Innovation
    • Title Advanced Research Activities in Biomedical Technology and Agri-food; Acronym: ΒΙΤΑΔ. FORTH
    • Funding Source Hellenic Ministry of Finance and Development; PA 2014-2020/ Competitiveness, Entepreneurship & Innovation
    • Contract Number MIS 5002469
    • Budget for FORTH: 2.319.500 €. Budget for IMBB-BR: 600.000 €; Budget for team:
    • Duration 08/09/2017-08/09/2020

    Additional Info

    • Programme Human Resources Development, Education and Lifelong Learning: Strengthening human research potential through doctoral research
    • Title Molecular mechanisms of asymmetric cell division during stem cell differentiation
    • Funding Source ΙΚΥ (State Scholarship Foundation); Type of Grant: PA 2014-2020/Human Resources Development, Education and Lifelong Learning: Strengthening human research potential through doctoral research. Thesis Supervisor: Theodore FOTSIS; Ph.D Student: Evangelos DROUGKAS; Host Organisation: University of Ioannina
    • Contract Number SPA00225-10
    • Budget (for the team): 23.391 €
    • Duration 01/05/2018–21/01/2020

    Additional Info

    • Programme Human Resources Development, Education and Lifelong Learning: Strengthening human research potential through doctoral research
    • Title Molecular Mechanisms of VEGF in Vasculogenesis and Applications in Regenerative Medicine
    • Funding Source ΙΚΥ (State Scholarship Foundation); Type of Grant: PA 2014-2020/Human Resources Development, Education and Lifelong Learning: Strengthening human research potential through doctoral research. Thesis Supervisor: Theodore FOTSIS; Ph.D Student: Maria MARKOU; Host Organisation: University of Ioannina
    • Contract Number MIS 5000433
    • Budget (for the team): 29.408 €
    • Duration 09/12/2019–08/12/2019

    Additional Info

    • Programme Human Resources Development, Education and Lifelong Learning: Strengthening human research potential through doctoral research
    • Title Targeted Medications: Endocytosis, trafficking and Molecular Mechanism of Action
    • Funding Source ΙΚΥ (State Scholarship Foundation); Type of Grant: PA 2014-2020/Human Resources Development, Education and Lifelong Learning: Strengthening human research potential through doctoral research. Thesis Supervisor: Theodore FOTSIS; Ph.D Student: Anastasia KOUGIOUMTZI; Host Organisation: University of Ioannina
    • Contract Number MIS 5003404
    • Budget (for the team): 29.408 €
    • Duration 15/05/2017–15/10/2018

    Additional Info

    • Programme National Strategic Reference Framework (NSRF)
    • Title Treating the Rupture of Anterior Cruciate Ligament: Regeneration using Stem Cells and Tissue Engineering
    • Funding Source National Strategic Reference Framework (NSRF) 2007-2013 – Region of Epirus
    • Contract Number 346955
    • Budget (for the team): 147.922,25 €
    • Duration 01/08/2011 – 31/05/2014

    Additional Info

    • Programme Investigation of the role of Rho GTPases
    • Title Investigation of the role of Rho GTPases in the regulation of the genomic and non-genomic responses of cells to cytokines
    • Funding Source GRST
    • Contract Number PENED 2003/03ED688
    • Budget (for the team): Total Budget 180,000 €, for IMBB-BR 44,625 €
    • Duration 2006-2010

    Additional Info

    • Programme Research program for the development of research institutes
    • Title Kripis I: Biology, Biophotonics, and Health: Modern technological approaches and applications in the field of Biology, Photonics and Health.
    • Funding Source GSRT. Research program for the development of research institutes
    • Contract Number MIS 448301
    • Budget (for the team): Budget for IMBB-BR:.300,000 €; Budget for Fotsis 6,000€
    • Duration 2015-2017
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