Silicone Implant Shells Increase the Rate of Proliferation of Alk- but Not Alk+ Lymphoma Cells in an Engineered Biomimetic Breast Microenvironment (2020)

PURPOSE: The pathogenesis of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), an Alk-pathology, remains poorly understood. Our lab has demonstrated the power of studying BIA-ALCL behavior in a high-fidelity tissue engineered ex vivo biomimetic, 3-dimensional model. Herein we use this model to study the behavior of Alk+ Lymphoma cells, which characterize the most common type of ALCL, within an engineered breast microenvironment, to serve as an important comparator to the behavior of BIA-ALCL cells, which are Alk-. METHODS: Patient-derived breast tissue was processed for its component adipocytes, ductal organoids, and stromal vascular fraction. These were suspended within 50 µl of 0.3% Type I collagen matrix to which was added 200,000 cells/ml of Alk+ Lymphoma cells. These were then plated into 6 mm wells. As a control, Alk+ Lymphoma cells were also suspended within Type I collagen alone at the same seeding density without breast components (“collagen only”). Before plating, wells were lined circumferentially with 1 cm by 2 cm pieces of either textured, smooth, or no implant shell (dissected from the intact implant). Wells were imaged using confocal microscopy over 8 days. RESULTS: There was a significant difference in cell counts over 8 days between the 6 different groups (P = 0.002; R2 = 0.625). Cell proliferation over time in the biomimetic groups, regardless of the presence or absence of implant shell, was significantly greater than cell proliferation in the collagen only groups over the same time period (P < 0.001). Overall, cell counts trended downward in the collagen only groups over 8 days with a significant decrease in count starting at day 6. There was no difference in the rate of proliferation of Alk+ cells in the presence of silicone shells. This is similar to the proliferation seen in Alk- BIA-ALCL cells, which was significantly more robust in the biomimetic platform compared to collagen-only groups, regardless of implant shell type (P < 0.01). Unlike Alk+ cells, Alk- BIA-ALCL cells grew nearly 30% faster in textured and smooth shell biomimetic groups compared with biomimetic wells lacking an implant shell. CONCLUSIONS: Within a tissue-engineered 3-dimensional model of the breast microenvironment, Alk+ Lymphoma cells, which serve as an important comparator cell line to the study of Alk- BIA-ALCL, showed a significant increase in proliferation within the biomimetic groups only over 8 days, regardless of the presence or absence of implant shell. Comparatively, BIA-ALCL cells proliferated significantly more robustly within this platform in the presence of textured and smooth implant shell as well as biomimetic platform. These data suggest that there is thus something inherently unique to Alk- BIA-ALCL cells that drives proliferation in the presence of both biomimetic platform and silicone implant shell as the presence of a silicone implant shell does not drive increased proliferation of Alk+ Lymphoma cells. These data suggest that breast implant silicone shell in combination with the breast microenvironment may drive the growth of BIA-ALCL.