Abstract
Abstract Currently available invasion assays for study of cancer metastasis have limitations that led us to develop a novel system that provides a more flexible, quantifiable, and physiologically relevant method to study cancer cell invasion. The three-dimensional (3D) hyaluronic acid (HA) hydrogel invasion assay then was used to study HA receptor signaling as it occurs during prostate cancer metastasis to bone marrow. Our invasion assay uses the HA hydrogel which reflects the prevalence of HA in the bone marrow and its key role in the promotion of cancer cell motility and tissue invasion. The HA hydrogel spontaneously crosslinks via interaction of aldehyde and hydrazide groups, allowing for direct encapsulation of cells within the gel. This cell/gel construct is plated in a 12 mm tissue culture insert for construction of the invasion assay. The cells are situated on a single plane so that individual cell movement from that plane can be tracked. We show that our 3D HA hydrogel invasion assay allows for cell migration/invasion in response to a chemoattractant, fetal bovine serum (FBS), and that this movement is easily quantified using confocal microscopy techniques over a distance of up to 1 mm. The ability of cancer cells to invade the HA hydrogel depends on their expression of HA receptors and hyaluronidases; more highly invasive cell lines express HA receptors and hyaluronidases at higher levels. We will show that culture in the HA hydrogel triggers differential expression and/or compartmental translocation of HA receptor proteins and downstream effectors, all of which contribute to motility and metastasis. Ongoing work examines the role that a specific HA receptor, RHAMM, plays in prostate cancer metastasis, specifically how it activates Rho GTPases that increase cell motility. We will show how these physiologically relevant 3-D HA hydrogel invasion assays can be used to study such pathways. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 523.
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