A microfluidic-based device for study of transendothelial invasion of tumor aggregates in realtime

Abstract

Circulating tumor aggregates exhibit a high metastatic potential and could potentially serve as an important target for cancer therapies. In this study, we developed a microfluidic model that reconstitutes and is representative of the principal components of biological blood vessels, including vessel cavity, endothelium, and perivascular matrix containing chemokines. Using this model, the transendothelial invasion of tumor aggregates can be observed and recorded in realtime. In this study we analyzed the extravasation process of salivary gland adenoid cystic carcinoma (ACC) cell aggregates. ACC aggregates transmigrated across the endothelium under the stimulation of chemokine CXCL12. The endothelial integrity was irreversibly damaged at the site of transendothelial invasion. The transendothelial invasion of ACC aggregates was inhibited by AMD3100, but the adhesion of ACC aggregates to the endothelium was not affected by the CXCR4 antagonist. This model allows for detailed study of the attachment and transendothelial invasion of tumor aggregates; thus, it would be a useful tool for analysis of the underlying mechanisms of metastasis and for testing novel anti-metastasis agents.

Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation

“…cancer cell migration, adhesion (23), and extravasation (24,25). Recently, our group presented a microfluidic model to investigate the specificity of breast cancer metastasis to bone, providing quantitative data on cancer cell extravasation rate and reproducing the effects of the CXCL5-CXCR2 interaction between bone cells and metastatic breast cancer cells observed in vivo (26).…”

Tumour-on-a-chip: microfluidic models of tumour morphology, growth and microenvironment

“…Zhang et al [119] demonstrated that chemokine CXCL12 could stimulate salivary gland adenoid cystic carcinoma cells to extravasate through HUVEC endothelium. The stimulated extravasation can also be inhibited by CXCR4 antagonist AMD3100.…”

“…Common methods to create capillary lumen structures as microvasculatures include moulding the capillaries in hydrogels by needles or rods [95][96][97][98], by photoresists [99][100][101], by sacrificial carbohydrates [102] or creating lumens based on viscous fingering instabilities [103,104]. Alternatively, an endothelial vascular network as the microvasculature can be formed by endothelial sprouting in hydrogels [105][106][107][108][109][110][111][112], monolayer on ECM hydrogel [113][114][115] or on a porous membrane [116,117], and monolayer in microchannels [118,119] (figure 2l ).…”

A dual-docking microfluidic cell migration assay (D2-Chip) for testing neutrophil chemotaxis and the memory effect

“…Then the fMLP gradient was applied for cell migration experiment. Similar microfluidics-based strategy for transendothelial migration has been reported previously [60][61][62] . Our preliminary results consistently show that neutrophils can migrate into the 10 nM fMLP source channel through the barrier channel and an additional HUVEC layer (Fig.…”