 |
| Normal
breast cells organized in three
dimension (left), breast tumor
cells unable to form organized
tissue-like structure (middle),
reversion of tumor cells to near
normal appearance by extracellular
matrix (right). |
The extracellular matrix (ECM), the
network of proteins surrounding cells
in the body, long was believed to
function mainly as inert scaffolding
for tissue. But in the early 1980s,
Mina Bissell of Lawrence Berkeley
National Laboratory proposed that
the ECM is a key "signaling molecule"
crucial for the normal functioning
of cells. That is, the ECM is one
of the environmental factors (along
with hormones) that communicate with
a cell nucleus, modifying nuclear
structures and leading to selective
gene expression. Bissell's theory
implied that alterations in the ECM
or cellular responses to it could
lead to malignancy, a radical idea
at the time. Her experiments showed
that in standard cultures, cancerous
breast cells grew at the same rate
and took on the same flat appearance
as healthy breast cells. But when
ECM was added to the culture, the
healthy cells once again became plump
and round and began secreting milk,
whereas the cancerous cells grew wildly
into a tumorous mass. Bissell was
among the first to connect the regulation
of cell growth and development with
the cell's environment.
Scientific Impact:
The ECM theory has steadily gained
scientific acceptance and yielded
a growing volume of knowledge about
both normal and breast cancer cells.
Bissell?s work has greatly influenced
cell biology, a field in which cells
are studied as living entities that
take on specialized functions, organize
into communities, and interact with
their environment.
Social Impact: The
new understanding of the ECM provides
information essential to the diagnosis
and successful treatment of cancer.
This work suggests that, even after
cancer genes have been activated and
lesions have formed, it may still
be possible to reverse the process
and restore the cells to normal appearance
and function.
Reference: Chen
M, K Schmeichel, IS Mian, SA Lelièvre,
OW Petersen and MJ Bissell, "AZU-1:
A candidate breast tumor suppressor
and biomarker for tumorigenic reversion,"
Mol Biol Cell 11(4):1357-1367
(2000).
Bissell, MJ, VM Weaver, SA Lelièvre,
F Wang, OW Petersen and KL Schmeichel,
"Tissue structure, nuclear organization
and gene expression in normal and
malignant breast," Cancer Res.
(Suppl.) 59:1757s-1764s (1999).
Lelièvre, SA, V. M Weaver, J. A. Nickerson,
C. A. Larabell, A. Bhaumik, O. W.
Petersen and M. J. Bissell, "Tissue
phenotype depends on reciprocal interactions
between the extracellular matrix and
the structural organization of the
nucleus," Proc. Natl. Acad. Sci.
USA 95, 14711-14716 (1998).
Weaver VM, OW Petersen, F Wang, CA
Larabell, P Briand, C Damsky and MJ
Bissell, "Reversion of the malignant
phenotype of human breast cells in
three-dimensional culture and in vivo
using integrin blocking antibodies,"
J. Cell Biol. 137:231-246
(1997).
URL:
http://www.lbl.gov/lifesciences/CMB/Bissell.html
Technical Contact:
Dr. David Thomassen, Life Sciences
Division, Office of Biological and
Environmental Research, 301-903-9817
Press Contact: Jeff
Sherwood, DOE Office of Public Affairs,
202-586-5806
SC-Funding Office:
Office of Biological and Environmental
Research |
