Biomedical Engineering Reference
In-Depth Information
6.4.2.2 Cancer Cell Migration
Some cancer cells in primary tumors acquire the ability to penetrate and iniltrate surrounding
normal tissues in the local area or in distant sites ater becoming circulating tumor cells, forming
a new tumor. herefore, in the process by which cancer spreads to other organs, called
metasta-
sis
, cell migration needs to be activated and plays an important role. As with neutrophils, cancer
cells are also a convenient source of cells to study cell motility in general, because several cancer
cell lines exist and the cells exhibit high motility rates in response to commercially available fac-
tors. Hence, cancer cells have historically been the second-most popular choice of cells (behind
neutrophils) in BioMEMS chemotaxis studies.
In 1998, Jefrey Segall's group at Albert Einstein's College of Medicine in New York used
SAM hexadecanethiol micropatterns on a background of HEG-terminated alkanethiol to study
the chemotaxis of rat mammary carcinoma cells, in particular, the relationship between adhe-
sion and chemoattractant-stimulated lamellipod extension. When a cell was attracted into a
nonadhesive region with a pipette delivering EGF, it still extended lamellipods over the HEG-
derivatized areas but rapidly retracted them. he absence of cell-substrate contacts on the non-
adhesive areas (as determined by immunostaining of talin, one of the proteins that links the
cytoskeleton to integrins) indicated that lamellipod extension can occur without establishing
focal adhesions but requires focal adhesions to stabilize.
In 2004, the laboratory of Noo-Li Jeon (who coinvented the Dertinger gradient generator in
2001, see
Figure 3.74
, and was the irst author in the 2002 article on neutrophil chemotaxis using
Dertinger's generator, see
Figure 6.25
), then at the University of California, Irvine, CA, again used
the Dertinger gradient generator to probe the response of the breast cancer cell line MDA-MB-231
to various EGF gradients (
Figure 6.30
). Linear concentration gradients were not able to induce
chemotaxis, whereas a nonlinear polynomial gradient induced a chemotactic movement.
(a)
Nonlinear MCC
Medium
EGF/FITC
100
Y = Cx
4.2
50
0
0
160
200
400
Position across channel [µm]
(b)
Away from gradient
%
Toward gradient
100
50
0
50
100
0-25
0-50
0-100
FIGURE 6.30
Chemotaxis.of.cancer.cells.in.a.microluidic.gradient..(From.Shur-Jen.Wang,.Wajeeh.
Saadi,.Francis.Lin,.Connie.Minh-Canh.Nguyen,.and.Noo.Li.Jeon,.“Differential.effects.of.EGF.gradi-
ent.proiles.on.MDA-MB-231.breast.cancer.cell.chemotaxis,”.
Exp. Cell Res.
.300,.180-189,.2004..
Reprinted.with.permission.from.Elsevier.)
