University of Cyprus Advanced Post-doctoral Research Fellowship “NanoMechanical FingerPrints of Pancreatic Cancer” (PACA-FingerPrints), January 2019 – December 2020, Funding: €74 000

Project details

Fellow: Andreas Stylianou

Principal Investigator: Triantafyllos Stylianopoulos

Total Funding: EUR 74 000

Funding scheme: University of Cyprus Advanced Post-doctoral Research Fellowships

Coordinated in: Cyprus (University of Cyprus)

From 01/01/2019 to 31/12/2020

SUMMARY

Cancer progression is closely associated with changes in the mechanical properties and structure of both cancer and stromal cells and the extracellular matrix (ECM) that comprise a tumor. The “PACA-FingerPrints” project aims to investigate the NanoMechanical FingerPrints of pancreatic solid tumors so as to be potentially used as a biomarker for more accurate and early cancer diagnosis.

The project proposes a 2 step research plan:

■1st-step: in vitro study in cancer cells (2D models) and cancer cells cultured in three dimensional (3D) ECM -containing models based on collagen.

■2nd-step: in vivo/ex vivo study in mouse tumor models.

Through the proposed project the NanoMechanical FingerPrints of pancreatic cancer cells will be investigated in correlation with cell invasiveness and ECM composition. State-of-the-art Atomic Force Microscopy (AFM) techniques will be utilized as a novel tool for evaluating the malignancy of tumors]. The project also involves a number of other techniques to investigate cancer cell morphology and stress fiber formation as well as the expression of specific genes, in correlation to the NanoMechanical FingerPrints. The results are expected to provide new insights and a novel approach for cancer diagnosis since AFM measurements could be used to complement standard biopsy procedures, offering an objective, novel and quantitative diagnostic approach with the properties of a blind assay, allowing unbiased evaluation of the sample.

REFFERENCES

Stylianou A., V. Gkretsi, M. Louca, L.C. Zacharia and T. Stylianopoulos. Collagen content and extracellular matrix cause cytoskeletal remodelling in pancreatic fibroblasts. Journal of the Royal Society Interface [DOI: 10.1098/rsif.2019.0226].

Stylianou A., M. Lekka and T. Stylianopoulos. AFM Assessing of Nanomechanical FingerPrints for Cancer Early Diagnosis and Classification: from single cell to tissue level. Nanoscale [DOI: 10.1039/C8NR06146G].

Stylianou A., V. Gkretsi, and T. Stylianopoulos. Atomic Force Microscopy Nano-Characterization of 3D Collagen Gels with Tunable Stiffness. MethodsX  5:503-513 [DOI: 10.1016/j.mex.2018.05.009]

Stylianou A., V. Gkretsi and T. Stylianopoulos. Transforming Growth Factor-β modulates Pancreatic Cancer Associated Fibroblasts cell shape, stiffness and invasion. BBA  1862(7):1537-1546 [DOI: 10.1016/j.bbagen.2018.02.009].

Stylianou A., Gkretsi V., Patrickios C.S., Stylianopoulos T. Exploring the Nano-Surface of Collagenous and Other Fibrotic Tissues with AFM. In: Rittié L. (eds) Fibrosis. Methods in Molecular Biology, vol 1627. Humana Press, New York, NY [DOI: 0.1007/978-1-4939-7113-8_29].

Stylianou A., and T. Stylianopoulos. Atomic force microscopy probing of cancer cells and tumor microenvironment components. BioNanoScience 6(1): 33-46. [DOI: 10.1007/s12668-015-0187-4].

Gkretsi V., A. Stylianou, P. Papageorgis, C. Polydorou, and T. Stylianopoulos T. Remodeling components of the tumor microenvironment to enhance cancer therapy. Frontiers in Oncology 5: 214. [DOI: 10.3389/fonc.2015.00214].