Development of 3D Lymph Node Mimetic for Studying Prostate Cancer Metastasis

Abstract

Lymph node (LN) metastasis causes poor prognosis for patients with prostate cancer (PCa). Although LN-cells and cellular responses play a pivotal role in cancer metastasis, the interplay between LNcells and PCa cells is undetermined due to the small size and wide-spread distribution of LNs. To identify factors responsible for LN metastasis, a 3D cell culture biosystem was fabricated to simulate LN responses during metastasis. We first determined that LN explants previously exposed to highmetastatic PCa release substantially more chemotactic factors to promote metastatic PCa migration than those exposed to low-metastatic PCa. Furthermore, T-lymphocytes were found to produce chemotactic factors in LNs, among which, CXCL12, CCL21, and IL-10 were identified to have the most chemotactic effect. To mimic LN-microenvironment, Cytodex®beads were seeded with T-cells to produce LN-mimetic biosystem in both static and flow conditions. As expected, flow condition permitted prolonged cellular responses. Interestingly, when PCa cells with varying metastatic potentials were introduced into the system, it produced PCa-specific chemokines accordingly. Such This article is protected by copyright. All rights reserved.2 differential responses were caused by the cell:cell interations between metastatic PCa cells and Tcells. These results support that the LN mimetic can help in analyzing the processes underlying metastasized LNs and for testing various treatments to reduce cancer LN metastasis.

Chemokine releasing particle implants for trapping circulating prostate cancer cells

“…The intravenous injection model demonstrates the similarity of cancer cell distribution in mice and PCa patients, except in bone metastasis 6,49 . However, we create a chemokine-releasing implant made of soft natural material to prove our hypothesis that our cell-free cancer trap has the potential to compete with organ metastasis once the cancer cells enter the circulation system in vivo, after our previous study elucidates the mechanism of cancer migration from an in vitro artificial lymph node model 50 . Bone metastasis occurs in stiff bone structure with various types of cells (osteoclast, osteoblast) and chemokines (TGFβ, RANKL and VEGF) 51,52 .…”

“…Electrospun fiber networks have been shown to trap cancer cells from human blood 54 . Metastatic lymph nodes are shown recently to promote the migration of KD cells but not PC3 50 . Porous scaffolds made of poly(lactide-co-glycolide) have been found to recruit breast cancer cells and subsequently reduce the tumor burden within solid organs 55 and animal survival 56 .…”