Investigating the Effect of Astrocytes and PDGFB Expression on Breast Cancer Tumorspheres Using 3D In Vitro Models
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Date
2024-05
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The Ohio State University
Abstract
Breast cancer (BC) is the most diagnosed cancer in females. Triple-negative BC (TNBC), is a subtype of BC, often metastasizes to the brain leading to difficulties in treatments due to the blood-brain barrier (BBB) and the brain tumor microenvironment (TME) resulting in low survival rates. Thus, the development of a 3D in vitro biomimetic model is critical for the exploration of mechanisms aiding BCBM. Astrocytes contribute to tumor progression and express the receptor for platelet-derived growth factor B (PDGFB), which has also been found to contribute to BCBM. Here, we utilize a 3D collagen 1 (Col 1) - hyaluronic acid (HA) hydrogel model developed and validated by Winter Lab (Cui et al.) to mimic the brain TME. Aim 1 was to investigate BC tumorsphere growth and migration in the presence of astrocytes. Aim 2 was to investigate BC tumorsphere growth and migration with BC cells not expressing and overexpressing PDGFB with and without astrocytes. We found the presence of astrocytes and PDGFB expression decreased the sphere size and migration capacity of BC tumorspheres. The presence of astrocytes dispersed around BC tumorspheres resulted in the recruitment of astrocytes to the tumorsphere surface and differences in migration patterns and collagen remodeling were observed when BC tumorspheres were in the presence of astrocytes. Overall, the findings indicate the presence of astrocytes and PDGFB expression results in decreased migratory capabilities of BC cells.
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Keywords
Breast Cancer, In Vitro Models, Tumorspheres, Breast Cancer Brain Metastasis, Astrocytes, Platelet Derived Growth Factor