A novel breast cancer model of early stage invasion

Citation for published version (APA):Sleeboom, J. J. F., Sahlgren, C., & den Toonder, J. M. J. (2016). A novel breast cancer model of early stageinvasion: using microfluidic methods to mimic a heterogeneous physical tumor microenvironment.

Document status and date:Published: 15/12/2016

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Download date: 19. Feb. 2021

The key biophysical property this model captures is the heterogeneous ECM

composition before invasion: Initially, cancer cells reside in a soft basement membrane

before invading the fibrous and stiffer stromal ECM [2]. A microfluidic bottom-up

fabrication approach enables the generation of this environment.

A novel breast cancer model of

early stage invasion

Using microfluidic methods to mimic a heterogeneous physical tumor microenvironment

Jelle J. F. Sleeboom1,2

Cecilia Sahlgren1,3

Jaap M. J. den Toonder2

1Soft Tissue Biomechanics & Engineering,

Eindhoven University of Engineering2 Microsystems group, Eindhoven

University of Technology3 Turku Centre for Biotechnology, Åbo

Akademi and Turku University

/ Soft Tissue Biomechanics & Engineering / Microsystems

The majority of breast cancer deaths are not caused by the primary tumor, but by metastasis to other organs

[1]. However, the mechanisms that underlie the first stage of metastasis, the invasion of cancer cells into

surrounding tissue remain elusive, due to the complexity of the cellular, biochemical, and biophysical

interactions in cancer tissue. In this work, we propose a novel in vitro breast cancer model that focuses on

dissecting the influence of the biophysical properties of the extracellular matrix (ECM) on the onset of cancer

invasion. Based on microfluidic technology, it will provide us with the necessary tools to independently vary

different material and cell properties, while it provides the cells with a physiologically relevant environment.

BO

TT

OM

-UP

FA

BR

ICA

TIO

N

Matrigel

Cancer

cell

Oil

Medium

Oil

Collagen

Oil

Matrigel is employed as a model for the basement membrane, and collagen I is used as a

model for the stromal ECM. Preliminary data shows a spherical micro-tumor invading the

collagen that surrounds the Matrigel environment between day 3 and 8.

Microfluidic high-throughput

encapsulation of single MDA-MB-231

breast cancer cells in Matrigel droplets.

100 µm

d3 d5 d8

The beads are retrieved from the oil and

transferred to cell culture medium. Not all beads

contain cells.

[1] Aceto, N., et al. (2014). Circulating tumor cell clusters are precursors of

breast cancer metastasis. Cell, 158(5), 1110–1122.

[2] Yu, H., et al. (2011). Forcing form and function: Biomechanical regulation of

tumor evolution. Trends in Cell Biology, 21(1), 47–56.

The beads are embedded in a

collagen I hydrogel without loss of

material or mixing, as shown by a

CNA35-OG probe for collagen.

CNA35-OG100 µm100 µm

medium

oil

Future work will focus on developing

and optimizing the shown fabrication

methods to increase yield and control.

Including:

• Microfluidic bead retrieval

• Microfluidic encapsulated cell sorting

• Microfluidic embedding in collagen

beads

A single cell

Cells in matrigelOil channels 100 µm

4

3

2

1