Microfluidic co-culture system for cancer migratory analysis and anti-metastatic drugs screening

Abstract

Tumour metastasis is an important reason for cancer death, and cancer cell migration is an important step in the process of tumour metastasis. Studying cancer cell migration is of great significance. Here, we present a novel microfluidic co-culture system and establish mild, moderate and severe cancer models by using HMEpiC and MDA-MB–231 cells to study cancer cell migration and anti-cancer drug screening. Using this device, we achieved high cell viability (over 90%) and a stable analysis of the migration ability of cancer cells. We observed that the density of the cancer cells determined the probability of the occurrence of metastatic cells and that the induction of normal cells affected the metastatic velocity of each cancer cell. We verified that the increase in the migration ability of MDA-MB-231 cells co-cultured with HMEpiC cells was relative to the increased secretion of IL-6 and that this was verified by an IL-6 inhibitor assay. This co-culture also led to decreased CK-14 secretion and morphological changes in HMEpiC cells. Finally, significant inhibition of paclitaxel and tamoxifen on cancer migration was observed. Taken together, our microfluidic device could be a useful tool for the quantitation of the migratory capability and anti-metastatic drug screening.

Vascularized microfluidic platforms to mimic the tumor microenvironment

“…Sung et al, ; K.E. Sung & Beebe, ; Ma, Middleton, You, & Sun, ; Mi et al, ; Soleimani et al, ; Staton et al, ; Yamada & Cukierman, ; Zhang & Radisic, ; Zheng et al, ). Some of the features not simulated in 2D culture include but are not limited to cell‐cell and cell‐matrix signaling, transport studies, and impact of mechanical and chemical gradients on cellular response.…”

“…Groups have utilized subtractive and additive tissue engineering processes to form microfluidic collagen scaffolds (Bettinger, Borenstein, & Tao, ; Bhatia & Ingber, ; Peela et al, ; Tien, ). Scaffolds with complex microfluidic networks have also been formed using additive methods of combining layers of natural materials formed with lithographic techniques and have been used to investigate various behaviors such as cell‐cell interactions during angiogenesis or metastasis, extravasation of breast cancer cells and interactions with the endothelium (Bhatia & Ingber, ; Bischel, Young, Mader, & Beebe, ; Farahat et al, ; Ghousifam et al, ; Jeon et al, ; Lee et al, ; Mi et al, ; Nagaraju et al, ; Peela et al, ; Price et al, ; Soleimani et al, ; Song et al, ; Y. Ma et al, ; Zheng et al, ). While these microfluidic devices have provided insight into tumor behavior, the in vitro platforms consist of small number of cells limiting the use of biological assays such as polymerase chain reaction or enzyme‐linked immunosorbent assay, or they lack a continuous endothelium failing to recapitulate the in vivo tumor microenvironment.…”

“…Groups have utilized subtractive and additive tissue engineering processes to form microfluidic collagen scaffolds (Bettinger, Borenstein, & Tao, 2012;Bhatia & Ingber, 2014;Peela et al, 2017;Tien, 2014). Scaffolds with complex microfluidic networks have also been formed using additive methods of combining layers of natural materials formed with lithographic techniques and have been used to investigate various behaviors such as cell-cell interactions during angiogenesis or metastasis, extravasation of breast cancer cells and interactions with the endothelium (Bhatia & Ingber, 2014;Bischel, Young, Mader, & Beebe, 2013;Farahat et al, 2012;Ghousifam et al, 2017;Jeon et al, 2015;Lee et al, 2014;Mi et al, 2016;Nagaraju et al, 2018;Peela et al, 2017;Price et al, 2008;Soleimani et al, 2018;Song et al, 2009;Y. Ma et al, 2018;Zheng et al, 2012).…”

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

“…Aside from having a lower cost and faster processing speed, microfluidic chips require a much smaller sample volume. Furthermore, these chips can be customized to monitor the effects of anti-cancer drugs on any number of parameters, including cell migration [188]. Specifically, Zhang et al developed a microfluidic device with 3120 different microchambers in which cell density was varied throughout the chambers, and the average migration velocity and the percentage of migrating cells were quantified.…”

Microfluidic Tumor-mimicking In Vitro Cell Culture Methods

“…2d) for metastasis studies and anti-metastatic drug screening on cancer cells with different degrees of aggressiveness (mild, moderate, severe). [15] Using a microfluidic device, it is possible to co-culture more than two types of cells at the same time. Liu et al simulated a bladder cancer microenvironment by co-culturing four cell types (fibroblasts, bladder cancer cells, macrophages and endothelial cells) in 3D matrigel.…”