ESTRO 2024 - Abstract Book

S5406

Radiobiology - Tumour biology

ESTRO 2024

This finding was further supported by the pancreatic-specific stoma, highlighting the key role of TGF- . MIA-PSC-S’s spheroids appeared more compact and resembled smooth, perfect circles (Figure 1, AR: 1.051 ± 0.164 with TGF- , 1.722 ± 0.995 without TGF- , p < 0.1). On the vascular side, we successfully achieved the formation of a pancreatic-specific microvascular network using pancreatic endothelial cells after 7 days in 2 out of 5 considered conditions. Cells were uniformly distributed in the external channel of the chip. Among the tested cases, the optimal cell ratio and density for PECs and PSCs were found to be 1:1 ratio and 4.5 M/ml cell density. We thereby demonstrated the possibility of recreating a pancreatic specific microvascular network in-vitro (Figure 1).

Conclusion:

We presented the proof-of-concept for PDAC on a chip, leveraging a 3D environment in a microfluidic chip (Figure 1). This device integrates a pancreatic-specific microvasculature with a PDAC-specific microenvironment. Given the previous evidence on chip compatibility with radiation [5,6], such a device paves the way for radiobiological tumor models on-chip considering tissue and tumor-specific environments.

Keywords: Tumor-on-chip, pancreatic cancer, microvasculature

References:

1. Kleeff, J. et al. Pancreatic cancer. Nat Rev Dis Primers 2, 16022 (2016).

2. Mizrahi, J. D., Surana, R., Valle, J. W. & Shroff, R. T. Pancreatic cancer. The Lancet 395, 2008–2020 (2020).

3. Chitty, J. L. et al. A first-in-class pan-lysyl oxidase inhibitor impairs stromal remodeling and enhances gemcitabine response and survival in pancreatic cancer. Nat Cancer 4, 1326–1344 (2023).

4. Chen, M. B. et al. On-chip human microvasculature assay for visualization and quantification of tumor cell extravasation dynamics. Nat Protoc 12, 865–880 (2017).

5. Guo, Z. et al. Validation of a Vasculogenesis Microfluidic Model for Radiobiological Studies of the Human Microvasculature. Adv Mater Technol 4, 1–12 (2019).

6. Possenti, L. et al. OC-0094 Radiobiological models for microvascular damage including functional impairment of capillary wall. Radiotherapy and Oncology 182, S57–S58 (2023).

Acknowledgments

This work was supported by the AIRC Investigator Grant, no. IG21479.