“Cell
migration represents a key aspect of cancer metastasis,” said
Konstantinos Konstantopoulos, professor and chair of the Department of
Chemical and Biomolecular Engineering at Johns Hopkins University.
Konstantopoulos was among the invited faculty speakers for the 2012
NanoBio Symposium.
Cancer
metastasis, the migration of cancer cells from a primary tumor to other
parts of the body, represents an important topic among professors
affiliated with Johns Hopkins Institute for NanoBioTechnology.
Surprisingly, 90% of cancer deaths are caused from this spread, not from
the primary tumor alone. Konstantopoulos and his lab group are working
to understand the metastatic process better so that effective
preventions and treatments can be established. His students have studied
metastatic breast cancer cells in the lab by tracking their migration
patterns. The group has fabricated a microfluidic-based cell migration
chamber that contains channels of varying widths. Cells are seeded at
one opening of the channels, and fetal bovine serum is used as a
chemoattractant at the other opening of the channels to induce the cells
to move across. These channels can be as big as 50 µm wide, where cells
can spread out to the fullest extent, or as small as 3 µm wide, where
cells have to narrowly squeeze themselves to fit through.
A
current dogma in the field of cell migration is that actin
polymerization and actomyosin contractility give cells the flexibility
they need to protrude and contract across a matrix in order to migrate.
When Konstantopoulos’s students observed cells in the wide, 50 µm-wide
channels, they saw actin distributed over the entirety of the cells, as
expected. They also observed that when the cells were treated with drugs
that inhibited actin polymerization and actomyosin contractility, they
did not migrate across the channels, also as expected.
However,
when the students observed cells in the narrow, 3 µm-wide channels,
they were surprised to see actin only at the leading and trailing edges
of the cells. Additionally, the inhibition of actin polymerization and
actomyosin contractility did not affect the cells’ ability to migrate.
“Actin
polymerization and actomyosin contractility are critical for 2D cell
migration but dispensable for migration through narrow channels,”
concluded Konstantopoulos. The data challenged what many had previously
believed about cell migration by showing that cells in confined spaces
did not need these actin components to migrate.
These
findings are indeed important in the context of cancer metastasis,
where cells must migrate through a heterogeneous environment of both
wide and narrow areas. Konstantopoulos’s data gives a better mechanistic
understanding of the different methods cancer cells use to migrate in
diverse surroundings.
Future
studies in the Konstantopoulos lab will focus on how tumor cells decide
which migratory paths to take. INBT-sponsored graduate student Colin
Paul has developed an additional microfluidic device that contains
channels with bifurcations. He hopes to determine what factors guide a
cell in one direction versus another. The Konstantopoulos lab hopes to
continue to understand exactly how tumor cells migrate so that new
therapies can eventually be developed to stop metastasis.
Source: Johns Hopkins University
