Abstract
We have developed a microfluidic-based culture chip to simulate cancer cell migration and invasion across the basement membrane. In this microfluidic chip, a 3D microenvironment is engineered to culture metastatic breast cancer cells (MX1) in a 3D tumor model. A chemo-attractant was incorporated to stimulate motility across the membrane. We validated the usefulness of the chip by tracking the motilities of the cancer cells in the system, showing them to be migrating or invading (akin to metastasis). It is shown that our system can monitor cell migration in real time, as compare to Boyden chambers, for example. Thus, the chip will be of interest to the drug-screening community as it can potentially be used to monitor the behavior of cancer cell motility, and, therefore, metastasis, in the presence of anti-cancer drugs.
Highlights
Metastasis is a leading cause of death in patients with malignant neoplasms [1]
In our microfluidic cancer cell migration model, we observed that MX-1 cells were able to invade across the collagen barrier into the side perfusion channels within 45 h (Figure 2A, Supplementary Video S1)
We were able to observe collective motility where cells retained their cell-cell contacts and invade as a group (Figure 2A). This mode of cancer cell motility has previously been observed in animal models only and is poorly understood because in vitro models have not been successful in modeling such motility [8,29]
Summary
Metastasis is a leading cause of death in patients with malignant neoplasms [1]. The mechanism of metastasis has been under intense research and may translate into effective cancer therapies [2,3,4]. It involves the loss of cell adhesion from the primary tumor, increased cell motility and invasion across the basement membrane into the blood capillary (intravasation), systemic circulation and, extravasation into surrounding tissues [5]. The assays for cancer metastatic potential are typically pursued in in vivo models since they have all the necessary cues essential for successful metastasis [6,7]. It is difficult to isolate and study the multi-factorial processes contributing to metastasis. In vitro models allow for more controlled experimentation to better understand specific processes, such as migration and invasion, leading to cancer metastasis [9]
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