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Cytokine-induced immune cell migration towards tumour cells in a microchip environment
KTH, School of Engineering Sciences (SCI).
KTH, School of Engineering Sciences (SCI).
2016 (English)Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
Abstract [en]

The purpose of this project was to study the migration patterns of human immune

cells in response to human renal cancer cells. This is useful in the study of

different cancer treatments and the body’s own response to cancer. Cancer cells can

release cytokines which can be detected by immune cells with the correct receptors.

The specific type of immune cell that was studied, was the type of lymphocyte

called Natural killer cell, abbreviated to NK cell. These lymphocytes have the

characteristics that they can differentiate between a cancer cell and a healthy cell,

and then have the capability to kill the cancer cell by different means.

On the surface of cells there exist receptors. These receptors can interact with

signal molecules in the environment near the cell. In this study the effect on the migration

caused by the interaction between the receptor CXCR2 and the chemokine

CXCL2 have been studied. This was done by transfecting some NK-92 cells with

the receptor CXCR2 and the rest with the receptor NGFR then subjecting them

to a CXCL2 chemokine gradient. This gradient originated from human renal cancer

cells known to produce this chemokine. The specific cancer cells used was the

human renal cancer cell line 786-0 which NK-92 cells are known to have the ability

to kill when coming in contact with them. It is because of this trait it is of interest

to study if the average movement is altered significantly by this receptor induced

movement compared to the control NK-92 NGFR.

To determine if a significant difference in preferred direction of migration could

be discerned between the NK cells expressing either the receptor CXCR2 or NGFR,

two analytic methods were devised and applied. The first method was a visualization

of the cell migration in the direction of the chemokine gradient, this analyze

had no quantitative properties but served as way to determine a general migration.

The second, and more precise method involved 3D cell identification, cell tracing,

and quantifying the migration. This method yielded quantifiable results that could

be analyzed further.

A biocompatible microchip with a small passage was utilized to study the migration

of the NK cells subjected to this chemokine gradient. Two different approaches

to this problem were made. The first approach was to seed the cells onto the chip

in a fluid and observe the migration of the sedimented cells the two dimensional

surface the glass bottom of the chip constituted. After several attempts with the

fluid approach the conclusion was made that because the NK-92 cells aren’t adherent,

fluid flows were found to be the main cause for the most of the NK-92 cells

movement. A few attempts were made to stop the fluid from flowing over the passage

by utilizing a plug placed in the center of the passage during the seeding of

the cells and removed before the experiment, but this was without success. Since

this flow made all unassisted migration by the cells impossible, no useful data could

be obtained from this method. This introduces the second approach which was to

suspended the cells in collagen. In these experiment no apparent movement by the

NK-92 cells was observed that could originate from fluid movement but did instead

seem to be unassisted cell migration.

It was found that in an open fluidic environment, fluidic phenomena preponderated

the cells own migration, and in the collagen environment the cell migration

was to small to yield any obvious results.

The analytic methods devised to trace cells and measure the cell migration

worked well and gave quantifiable results. In the 3D experiments these methods

were able to trace the NK cells and study the migration of the cells with different

receptors.

Place, publisher, year, edition, pages
2016. , 28 p.
National Category
Engineering and Technology
Identifiers
URN: urn:nbn:se:kth:diva-195835OAI: oai:DiVA.org:kth-195835DiVA: diva2:1045587
Available from: 2016-11-10 Created: 2016-11-10Bibliographically approved

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