Closer to nature in vitro: organ-specific extracellular matrix-based three dimensional models of cancer

Nadort A1,2, Iqbal S1,2, Parker L1,2, Packer N1,2, Goldys E2,3 and Guller A2,3

  1. Macquarie University, NSW 2109, Australia.
  2. ARC Centre of Excellence for Nanoscale BioPhotonics, Australia.
  3. University of New South Wales, NSW, 2032, Australia.

Successful clinical translation of techniques and therapies to detect and treat cancer needs controlled, ethical and practical lab-based tumour models that more accurately represent the biological reality. We repurposed tissue engineering methodology to create a biochemically and structurally authentic environment for in vitro cell culturing and developed an organ-specific three-dimensional (3D) model of cancer closely simulating real tumour tissue. We obtained acellular organ-specific tissue scaffolds with preserved extracellular matrix composition and structure by original decellularization protocols, followed by seeding and culturing the desired cancer cells to obtain tumour tissue engineering constructs (TECs). We focused on aggressive and problematic cancers such as high-grade brain cancer (glioblastoma mulitforme, GBM) and triple negative breast cancer (TNBC) known for its high rate of hepatic metastasis. Following our protocols, we created brain-TECs of GBM cells (human, U87 and U251) and control undifferentiated neurons (rat, PC12), as well as liver-TECs of TNBC cells (human, MDA-MB-231) to mimic hepatic metastasis. We extensively characterized the tumour TECs and compared the hallmarks of tumour progression, such as the growth dynamics, migration behavior, cell morphology, metastatic colonization, angiogenic potential and drug sensitivity, to 2D cultures and control TECs. Our results show a novel biologically accurate, living 3D tumour model, revealing ECM-specific cellular behavior that enables a more realistic study of tumour biology and therapeutic response. Our organ-specific tumour TECs can be used as a tool to improve the detection and treatment of cancer, and represent a sustainable approach to fill the gap between conventional 2D cell cultures, animal studies and clinical trials.