(655d) Interactions of Circulating Tumor Cells with Their Environment during Microfluidic Flows

Metastasis is a stage in cancer where tumor cells spread throughout the body
and form new cancer sites, distant from the original one. It is associated with poor
prognosis and is hard to diagnose early on. The migrating cancer cells are called
circulating tumor cells (CTCs) and their transitioning is characterized by complex
metabolic changes and the emergence of unique interactions with each other and their
environment [1]. Besides blood vessels, understanding the flow of CTCs is important in
microfluidic devices as promising platforms for the isolation and analysis of CTCs [1-3].
Further, there exists growing evidence that a subset of CTCs tend to form aggregates
that are even more dangerous than their single-cell counterparts [1, 4]. Detection and
further research on CTC clusters is another critical step in cancer research that
inherently involves microfluidic environments [1, 4].
Our group previously developed computational models of CTCs with varying clustering
propensities with and without external microfluidic flow [5, 6]. The most recent
framework included a combination of collective motion of cells with explicit mechanistic
bonding into physical aggregates [6]. Here we leverage this model to include complex
interactions with vessel walls and other types of cells. In particular, we focus on CTC
adhesion and rolling over solid surfaces, emulating a critical step in CTC invasion of
distant tissues [7, 8]. The model is further enriched by the introduction of interactions
with other types of cells present in blood, including red blood cells and immune
response constituents [1, 4, 8, 9]. We calibrate and validate our model with available
experimental data [8, 10] and show that it leads to unique conclusions about CTC
transport and dynamics in the circulatory system and other similar microfluidic
environments.

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Chandrasekaran, S., McGuire, M.J., Carr, R.T., Baker-Groberg, S.M., Rigg, R.A. and
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Scaglione, S., 2021. High blood flow shear stress values are associated with circulating tumor
cells cluster disaggregation in a multi-channel microfluidic device. PLOS One, 16(1),
p.e0245536.