Scaffold-integrated microchips for end-to-end in vitro tumor cell attachment and xenograft formation

Microfluidic technologies have substantially advanced cancer research by enabling the isolation of rare circulating tumor cells (CTCs) for diagnostic and prognostic purposes. The characterization of isolated CTCs has been limited due to the difficulty in recovering and growing isolated cells with high fidelity. Here, we present a strategy that uses a 3D scaffold, integrated into a microfludic device, as a transferable substrate that can be readily isolated after device operation for serial use in vivo as a transplanted tissue bed. Hydrogel scaffolds were incorporated into a PDMS fluidic chamber prior to bonding and were rehydrated in the chamber after fluid contact. The hydrogel matrix completely filled the fluid chamber, significantly increasing the surface area to volume ratio, and could be directly visualized under a microscope. Computational modeling defined different flow and pressure regimes that guided the conditions used to operate the chip. As a proof of concept using a model cell line, we confirmed human prostate tumor cell attachment in the microfluidic scaffold chip, retrieval of the scaffold en masse, and serial implantation of the scaffold to a mouse model with preserved xenograft development. With further improvement in capture efficiency, this approach can offer an end-to-end platform for the continuous study of isolated cancer cells from a biological fluid to a xenograft in mice.

VCAM-1 and VAP-1 recruit myeloid cells that promote pulmonary metastasis in mice

Key PointsMetastatic tumor cell attachment induces endothelial VCAM-1 and VAP-1. VCAM-1 and VAP-1 promote metastatic tumor cell survival by recruiting myeloid cells, pointing to VAP-1 as a therapeutic target.

LYVE-1 enhances the adhesion of HS-578T cells to COS-7 cells via hyaluronan

Purpose: Lymphatic vessel endothelial hyaluronan receptor (LYVE-1), a specific molecular marker for lymph systems, has only one known ligand, hyaluronan (HA). Many studies have reported that HA, on the surface of tumor cells, is associated with the metastatic behavior of cancer cells. The interaction of LYVE-1 with HA may facilitate tumor cell attachment and enhance dissemination of tumor cells to lymph nodes. The aim of this study was to explore the biological function of LYVE-1 and to determine whether the interaction between LYVE-1 and HA was directly involved in the adhesion of tumor cells to lymphatic vessels. Methods: COS-7 cells were transfected with cDNA encoding LYVE-1 and expressed LYVE-1 assembled exogenously added HA. A high HA-expressing breast cancer cell line, HS-578T, was chosen to be the upper layer of cells that adhered to a lower layer of COS-7LYVE-1(+), COS-7pegfp-N1, or COS-7 cells for the adhesion analyses. The mechanism of adhesion was investigated by an experiment in which the HA on the surface of HS-578T cells was digested by Streptomyces hyaluronidase before the HS-578T cells were allowed to adhere to COS-7LYVE-1(+) cells. Results: Results showed that more adhesion was observed between HS-578T and COS-7LYVE-1(+) cells, while less adhesion was observed between HS-578T cells and either COS-7pegfp-N1 or COS-7 cells (p < 0.01). Decreased HA on the HS-578T cell surface could reduce the adhesion of HA-578T cells to COS-7LYVE-1(+) cells.suggesting that this adhesion might be mediated through HA. Conclusion: Our results suggest that LYVE-1 allows the adhesion of tumor cells through the interaction of HA on the tumor cell membrane with LYVE-1.