Biological complexity: extracellular matrix activity (Introduction)

by David Turell , Tuesday, July 04, 2017, 14:55 (2699 days ago) @ David Turell

Cell culture studies indicate the extracellular matrix is not inert as thought, but actively controls gene expression and cell activity:

http://www.the-scientist.com/?articles.view/articleNo/48909/title/Location--Location--L...

"That thinking led her to propose, in 1982, that the microenvironmental influence is the ECM, which both chemically and physically interacts with cells. According to Bissell’s ‘dynamic reciprocity’ model, signals from the ECM traveled through transmembrane receptors to a cell’s interior and nucleus, altering its gene expression. “I began to think that the ECM played a role in tissue and organ specificity, because the cells all had the same genetic material, but I realized that there is no constitutive gene expression, that the context changes and so do the cells.”

"To provide evidence for the model, Bissell’s lab developed 3-D culture techniques, allowing differentiation and creation of at least partial tissue architecture of the mammary gland in culture. “If the cellular and tissue architecture is so important, I thought we should be able to take a malignant cell and change its structure and make it normal and also vice versa,” says Bissell. By the early 1980s, integrins—proteins that physically attach the ECM to the cell cytoskeleton—had been discovered. Valerie Weaver, a postdoc in Bissell’s lab, showed that blocking integrins with an inhibitory antibody could revert the malignant phenotype of human breast cancer cells in 3-D culture. Then, in collaboration with Zena Werb of the University of California, San Francisco, the labs showed that proteins called matrix metalloproteinases (MMPs), when upregulated, promote tumor formation, providing evidence that the ECM can encourage malignant transformation and proliferation. Six years later, the two labs revealed that signaling from the MMPs resulted in genomic instability in cells that led to malignancy.

" Bissell’s lab is still buzzing with excitement, continuing to bolster the validity of her dynamic reciprocity model. “When I would give talks and say that laminin [a large extracellular protein that is a major component of the basement membrane] is as important as p53, people would laugh. We have been working on the story of what laminin does for the last eight years, and it is almost complete,” says Bissell. “It probably will be considered one of my most important studies.”

"Over a period of 40 years, was instrumental in developing the field of tumor microenvironments
Developed the concepts that phenotype is dominant over genotype, that context matters, and that cellular and tissue architecture relays messages to cells
Used a “steady-state machine” she helped develop to show that the level of sugar in culture media determined whether chicken cells remained normal or displayed malignant metabolic patterns
In her model of dynamic reciprocity, proposed that the extracellular matrix directly signals to the nucleus and chromatin biochemically and mechanically to regulate gene expression  (my bold)
Developed three-dimensional culture techniques using basement membrane gels to study organ specificity in mammary organoids."

Comment: This scientist notes the automaticity of controls (note my bold) in cells from multicellular organisms. I am convinced bacteria are no different, except Shapiro's discovery that bacteria have extra controls over their DNA, since everything is in one cell