Abstract 4304: A microfluidic invasion assay to investigate the mechanisms involved in prostate cancer metastasis to bone
Authors: Lauren L. Bischel, Benjamin P. Casavant, David J. Beebe
Journal: Cancer Research (2012)

Abstract Background: The majority of cancer patient mortality can be attributed to the spread of the cancer to secondary sites. Bone represents one of the most preferential sites for metastases from prostate and other cancers. While there has been much investigation into the underlying mechanisms involved in the homing of prostate cancer metastases to bone, there is still much that remains to be elucidated. Methods: We present a microfluidic invasion assay that can be used to investigate the mechanisms by which prostate cancer cells metastasize to bone. The assay uses a controlled microenvironment with a simple readout to observe the formation of cellular protrusions during invasion. By flowing fluid through an extracellular matrix (ECM) hydrogel in a microfluidic channel, an ECM hydrogel with a continuous lumen patterned through the microfluidic channel can be formed. Cancer cells can then be seeded into the lumen and invasion of the cells into the ECM hydrogel can be quantitatively analyzed using microscopy after 24 hours. The assay can be altered to model invasion in different microenvironments by altering the ECM hydrogel composition and pre-seeding the channels with cell representative of a secondary site before the ECM coating is formed. Results: In cocultures of LNCaPs (a prostate cancer cell line) or C4-2B (a bone metastatic LNCaP derived prostate cancer cell line) in the lumen with MC3T3s (osteoblast cell line) pre-seeded on the side of the microchannel, the C4-2Bs invaded more readily than LNCaPs. When C4-2Bs in the lumen are cultured with MC3T3-E1s on the side of the microchannel an 8-fold increase in the percentage of invasive C4-2Bs was observed compared to C4-2B alone. A 5-fold increase in invasiveness was observed when C4-2Bs were cultured with conditioned media from a mixed culture of C4-2Bs and MC3T3-E1s. Conclusions: These results indicate that cross-talk between prostate cancer cells and osteoblasts could play a role in the targeting of prostate cancer metastases to bone. This assay offers several advantages over traditional macroscale invasion assays (e.g. transwell assays) including the capability to control and vary the matrix composition and to perform the assay with a smaller number of cells. The microchannels can be arrayed allowing many different conditions to be tested in a single platform. Additionally, the assay set-up can be performed with automated liquid handling systems further increasing the ability to assay different conditions in a high-throughput manner. These capabilities will allow in vitro studies not previously possible which could yield new insights into the mechanisms controlling prostate cancer cell homing to bone. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4304. doi:1538-7445.AM2012-4304