Periodic Reporting for period 1 - MYO-DESMOPLASIA (Modulating the behaviour of cancer myofibroblasts to control tumour desmoplasia)
Período documentado: 2015-06-01 hasta 2017-05-31
The specific research objectives of the project were: Research Objective 1: Development of a collagen based ECM model, with pre-determined topography and tunable stiffness. Research Objective 2: Characterization of the mechanical properties and behaviour of fibroblasts and myofibroblasts cultured in the ECM models as a function of TGFβ. Research Objective 3: gene expression analysis of fibroblasts and CAFs in the matrix models to identify genes responsible for ECM production as a function of TGFβ and correlate to cell mechanical properties.
Our results showed that CAFs present specific characteristic of the myofibroblasts phetotype, such as elongation and a-smooth muscle actin expression, while we demonstrated that CAFs have more lamellipodia and are softer compared to normal FBs. Also, it was revealed that TGFβ and collagen stiffness significantly affect CAFs basic morphodynamic characteristics, such as cell elongation, cell spreading, number of lamellipodia and stress fiber orientation, while this was not the case for normal FBs. For both FBs and CAFs it was found that TGFβ increase their stiffness in term of Young’s modulus values. Moreover, a significant correlation was revealed between cell spreading and RAC expression in both cell lines. Also, RhoA and ROCK expression was altered in CAFs after TGFβ treatment, which in combination with RAC expression is correlated to the increase in the number of lemellipodia, stress fiber orientation, cells’ mobility and stiffness. Although more research is needed to elucidate the exact involvement of TGFβ and ECM stiffness in desmoplasia, these findings provide new insights that need to be taken into consideration for understanding of desmoplasia or even for the development of novel therapeutic approaches for treating cancer having TGFβ as a target molecule.
Exploitation and dissemination
Conferences/forums and public engagement activities
-Stylianou, A, Stylianopoulos, T. (2016) ""Investigation of the effect of Tumor Growth Factor-β on Pancreatic Normal and Cancer Associated Fibroblasts"", Cyprus Researchers' Night 2016, 30 September, Nicosia, Cyprus (poster).
-Stylianou, A, Gkretsi, V. and Stylianopoulos, T. (2016) ""Effects of Tumor Growth Factor β on Pancreatic Cancer Associated Fibroblasts and Fibroblasts"", EUROAFMForum 2016, June, 22-24, 2016, Geneva, Switzerland (podium)
Journal Paper Publications (Peer-reviewed)
-Stylianou, A. (2017) ""Atomic Force Microscopy for Collagen-Based Nanobiomaterial"", Journal of Nanomaterials, art. id. 9234627
-Kontomaris, S.V and Stylianou, A. (2017) ""Atomic Force Microscopy for University Students, Application in Biomaterials"" European Journal of Physics, 38 (3)
-Stylianou, A. and Stylianopoulos, T. (2016) ""Atomic Force Microscopy Probing of Cancer Cells and Tumor Microenvironment Components"" BioNanoScience,6 (1), 33-46
-Gkretsi, V., Stylianou, A., Papageorgios, P., Polydorou, C. and Stylianopoulos, T. (2015) ""Remodeling components of the tumor microenvironment to enhance cancer therapy"" Frontiers in Oncology, 5 (214)
-Two research articles containing all the work performed during the period of the project is currently under preparation
-A book chapter is under publication: Stylianou, A., Gkretsi, V, Patrickios, C. and Stylianopoulos, T. ""Chapter 29: Exploring the nano-surface of fibrotic tissues with AFM"" In: Fibrosis: Methods and Protocols (Rittié L, ed), Springer.
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