Both factors can potentially be manipulatedeither to raise or lower the levels of growth factor or, as Asthagiri and colleagues showed in their paper, to raise or lower the contact-inhibition threshold.
In other words, Asthagiri explains, the team's research showed that it's possible to tune the systemto make cells more or less able to respond to a certain level of EGF by "playing with the extent of the contact the cells have with their neighbors."
One way to do that is to crowd the cells. "For instance," he says, "if you take a large number of cells and force them into the same area in which only a few cells are normally found, the cells become somewhat deaf to the growth factors. In order to get these cells to divide, you really have to crank up the level of growth factors they're exposed to."
You can achieve a similar result, Asthagiri adds, by creating cells that overexpress a protein called E-cadherin, which is a tumor suppressor protein that promotes adhesion of one cell to another. "This makes the cells less willing to divide," he notes, "which means they need a higher level of growth factor before they will divide."
The relationships between these competing influences "are really striking when you let them play out" under the influence of cell geography, says Asthagirithat is, when the cells grow as a multicellular cluster. The reality is that not all cells in a cluster are exposed to the same amount of inhibition. For instance, the cells in the center of the grouppressed against other cells on all sideswill experience more contact, and will require a larger amount of growth factor if they are to overcom
|Contact: Lori Oliwenstein|
California Institute of Technology