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