(D-138) Development of a Three-dimensional Model on a Chip of Multifocal and Multicentric Breast Cancer for Studying Multiple-tumor Interaction and Progression

Introduction:: Breast cancer has been the second leading cause of cancer-related death in women. It is estimated that 15- 25% of breast cancer cases are classified as multifocal (MF) or multicentric (MC). MF and MC breast cancers, compared with unifocal breast cancers, tend to be more aggressive and are associated with lower survival rates, higher recurrence, and lymph node metastasis.


Materials and Methods:: This project studied the interactive behaviors between multiple breast cancer tumors using an in vitro on-chip model combined of three -dimensional breast cancer spheroids and microfluidics technology. The chip includes SU-8 photoresist chessboard-like patterns deposited on a glass slide, and polydimethylsiloxane (PDMS) wells placed on top of the patterns to create a defined room for cell study. The chip has two major functions i) PDMS wells for homing breast cancer spheroids (Fig 1A, C) and ii) a chessboard-like pattern to facilitate the positioning of multiple spheroids (Fig 1B, D, E). This chip using spheroids embedded in collagen gel (Fig D, E, F) can simulate the microstructure of primary tumors within the collagen-rich extracellular matrix in the breast.


Results, Conclusions, and Discussions:: We determined that the MF/MC breast cancer spheroids moved across their extracellular matrix, shortening the distance between each other by 871.1±602.7 um and 765.846±547.7 um, for 3 and 2 MF/MC breast cancer spheroids respectively, over 72 hours. There was no significant change in individual breast cancer spheroid area over 72 hours, but in the multiple setup spheroids tended to merge into a larger one. Additionally, there was no significant difference in the area of cells sprouting away from the spheroid in MF/MC breast cancer spheroids and unifocal (single) breast cancer spheroids. This study helps broaden our understanding of the characteristics and invasive mechanisms of MF/MC breast cancer tumors, allowing us to better predict patient prognosis and suggest novel targets for breast cancer treatments in subsequent studies.


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