.........................
How breast cancer cells break free to spread in body
Date:
December 17, 2014
Source:
Georgia Institute of Technology
Summary:
More than 90 percent of cancer-related deaths are caused by the spread of
cancer cells from their primary tumor site to other areas of the body. A new
study has identified how one important gene helps cancer cells break free from
the primary tumor.
..........................
more than 90 percent of
cancer-related deaths are caused by the spread of cancer cells from their
primary tumor site to other areas of the body. A new study has identified how
one important gene helps cancer cells break free from the primary tumor.
A gene normally involved in the regulation of embryonic development can
trigger the transition of cells into more mobile types that can spread without
regard for the normal biological controls that restrict metastasis, the new
study shows.
Analysis of downstream signaling pathways of this gene, called SNAIL, could
be used to identify potential targets for scientists who are looking for ways
to block or slow metastasis.
"This gene relates directly to the mechanism that metastatic cancer
cells use to move from one location to another," said Michelle Dawson, an
assistant professor in the School of Chemical and Biomolecular Engineering at
the Georgia Institute of Technology. "If you have a cell that
overexpresses SNAIL, then it can potentially be metastatic without having any
environmental cues that normally trigger this response."
The study was sponsored by the National Science Foundation (NSF) and was
published December 9 in the Journal of the Federation of American
Societies for Experimental Biology (FASEB).
Previously, Dawson and Daniel McGrail, the lead author on the new study,
published a study showing how ovarian cancer cells respond to the mechanics of
their bodily environment. Their data showed that ovarian cancer cells are more
aggressive on soft tissues -- such as the fatty tissue that line the gut -- due
to the mechanical properties of this environment. The finding is contrary to
what is seen with other malignant cancer cells that seem to prefer stiffer
tissues.
In the new study, the researchers show how overexpression of the gene SNAIL
in vitro allows breast cancer cells to operate independently of the mechanics
of the environment inside the body. Growing evidence suggests that cancer cells
metastasize by hijacking the process by which cells change their type from
epithelial (cells that lack mobility) to mesenchymal (cells that can easily
move). In the new study, the researchers examined the biophysical properties of
breast cancer cells that had undergone this epithelial to mesenchymal
transition (through overexpression of SNAIL).
The research team measured the mechanical properties within the nucleus and
cytosol of breast cancer cells, and then measured the surface traction forces
and the motility of the cells on different substrates. They found that cells
became much softer, which could help them spread throughout the body.
Dawson's lab collaborated with the lab of John McDonald, a professor in the
School of Biology at Georgia Tech, to use microarray analysis to examine
changes in genes related to the observed biophysical changes. The researchers
found that regardless of the substrate that the cells were grown on, cells that
overexpress SNAIL look and act like aggressive cancer cells.
"We found that when the cells express SNAIL, they have biophysical
properties that are similar to what we see for an activated metastatic cancer
cell," Dawson said.
Although SNAIL triggers a transformation that helps cells move from the
primary tumor to the metastatic site, once the cell arrives at the metastatic
site and that tumor starts to grow, SNAIL no longer helps cancer progress.
Though becoming softer may help cells spread to the secondary site, they were
no longer sturdy enough to form a secondary tumor.
"The cells need to transfer back to the epithelial state so they can
withstand solid stress," Dawson said.
The researchers hope that their unique blend of microarray analysis and
characterization of physical changes in breast cancer cells undergoing
metastasis could aid the search for ways to block or slow the spread of cancer.
"We think this work has great potential to lead to a new approach to
cancer therapeutics," said McDonald, who is also the director of the
Integrated Cancer Research Center at Georgia Tech.
Story Source:
Journal Reference:
1. Michelle Dawson et al. SNAIL-induced
epithelial-to-mesenchymal transition produces concerted biophysical changes
from altered cytoskeletal gene expression. Journal of the
Federation of American Societies for Experimental Biology, December 2014
DOI: 10.1096/fj.14-257345 fj.14-257345
Lebih dari
90 persen kematian terkait kanker disebabkan oleh penyebaran sel-sel kanker
dari lokasi tumor primer mereka ke area lain dari tubuh. Sebuah studi baru
telah mengidentifikasi bagaimana satu gen penting membantu sel-sel kanker
melepaskan diri dari tumor primer........
......................
How breast cancer cells break free to spread in body
Date:
December 17, 2014
Source:
Georgia Institute of Technology
Summary:
More than 90 percent of cancer-related deaths are caused by the spread of
cancer cells from their primary tumor site to other areas of the body. A new
study has identified how one important gene helps cancer cells break free from
the primary tumor.
..........................
more than 90 percent of
cancer-related deaths are caused by the spread of cancer cells from their
primary tumor site to other areas of the body. A new study has identified how
one important gene helps cancer cells break free from the primary tumor.
A gene normally involved in the regulation of embryonic development can
trigger the transition of cells into more mobile types that can spread without
regard for the normal biological controls that restrict metastasis, the new
study shows.
Analysis of downstream signaling pathways of this gene, called SNAIL, could
be used to identify potential targets for scientists who are looking for ways
to block or slow metastasis.
"This gene relates directly to the mechanism that metastatic cancer
cells use to move from one location to another," said Michelle Dawson, an
assistant professor in the School of Chemical and Biomolecular Engineering at
the Georgia Institute of Technology. "If you have a cell that
overexpresses SNAIL, then it can potentially be metastatic without having any
environmental cues that normally trigger this response."
The study was sponsored by the National Science Foundation (NSF) and was
published December 9 in the Journal of the Federation of American
Societies for Experimental Biology (FASEB).
Previously, Dawson and Daniel McGrail, the lead author on the new study,
published a study showing how ovarian cancer cells respond to the mechanics of
their bodily environment. Their data showed that ovarian cancer cells are more
aggressive on soft tissues -- such as the fatty tissue that line the gut -- due
to the mechanical properties of this environment. The finding is contrary to
what is seen with other malignant cancer cells that seem to prefer stiffer
tissues.
In the new study, the researchers show how overexpression of the gene SNAIL
in vitro allows breast cancer cells to operate independently of the mechanics
of the environment inside the body. Growing evidence suggests that cancer cells
metastasize by hijacking the process by which cells change their type from
epithelial (cells that lack mobility) to mesenchymal (cells that can easily
move). In the new study, the researchers examined the biophysical properties of
breast cancer cells that had undergone this epithelial to mesenchymal
transition (through overexpression of SNAIL).
The research team measured the mechanical properties within the nucleus and
cytosol of breast cancer cells, and then measured the surface traction forces
and the motility of the cells on different substrates. They found that cells
became much softer, which could help them spread throughout the body.
Dawson's lab collaborated with the lab of John McDonald, a professor in the
School of Biology at Georgia Tech, to use microarray analysis to examine
changes in genes related to the observed biophysical changes. The researchers
found that regardless of the substrate that the cells were grown on, cells that
overexpress SNAIL look and act like aggressive cancer cells.
"We found that when the cells express SNAIL, they have biophysical
properties that are similar to what we see for an activated metastatic cancer
cell," Dawson said.
Although SNAIL triggers a transformation that helps cells move from the
primary tumor to the metastatic site, once the cell arrives at the metastatic
site and that tumor starts to grow, SNAIL no longer helps cancer progress.
Though becoming softer may help cells spread to the secondary site, they were
no longer sturdy enough to form a secondary tumor.
"The cells need to transfer back to the epithelial state so they can
withstand solid stress," Dawson said.
The researchers hope that their unique blend of microarray analysis and
characterization of physical changes in breast cancer cells undergoing
metastasis could aid the search for ways to block or slow the spread of cancer.
"We think this work has great potential to lead to a new approach to
cancer therapeutics," said McDonald, who is also the director of the
Integrated Cancer Research Center at Georgia Tech.
Story Source:
Journal Reference:
1. Michelle Dawson et al. SNAIL-induced
epithelial-to-mesenchymal transition produces concerted biophysical changes
from altered cytoskeletal gene expression. Journal of the
Federation of American Societies for Experimental Biology, December 2014
DOI: 10.1096/fj.14-257345 fj.14-257345
