The circuitry of a cancer cell alone does not explain everything about how tumors arise, according to premier molecular biologist Dr. Robert A. Weinberg, who spoke last night in a packed Filene Auditorium.
Part of the Medical School's Distinguished Lecture Series, Weinberg spoke about the research his laboratory has conducted on cancer formation in humans.
"What is the number of genetic changes necessary for cancer cell formation?" he asked. This question has been the driving force behind much of Weinberg's research. Through a variety of approaches, including the construction of a cancer cell by introduction of a defined set of mutant genes, Weinberg's lab has elucidated many of the pathways which lead to cancer when disturbed.
These pathways involve tumor suppressor genes as well as oncogenes, according to Weinberg.
In order for a tumor to arise, alterations in five distinct pathways or systems must occur. Scientists have not yet determined if there are more or fewer changes necessary. Research also does not explain how cancer cells become invasive -- or metastasize -- Weinberg said.
Eighty percent of all cancers arise from changes in epithelial cells, the cells in focus in the majority of cancer studies. Using the analogy of a stop sign, which he labeled a "mortality barrier," Weinberg said cancer cells differ from normal human cells in that they ignore such biological road signs, and thus proliferate indefinitely.
Surrounding epithelial cancer cells are stromal cells, cells habitually disregarded in the investigation of the cancer mechanism. Stromal cells are "essential contributors to tumor formation," according to evidence accumulated by Weinberg's lab.
Like the popular computer game StarCraft in which the player gathers minerals to produce marines and firebats, cancer cells recruit hoards of stromal cells to the future tumor site.
Weinberg's lab performed an experiment which demonstrated that a tumor forms faster when additional stromal cells are present.
Much of the research to date on cancer has been on mice, and this may in fact be a problem, Weinberg said. "There are differences in the wiring of mouse and human cells," he said. For instance, he said, humans go through 100,000 times more cell divisions in a lifetime than mice do. Many of the tests performed on rodents to determine whether a substance is carcinogenic to humans do not actually yield information about human cancer risk, Weinberg said.
In response to the realization of the disparities between human and mouse cells, Weinberg attempted to put human breast tissue in a mouse so as to have an experimental system for breast cancer research, specifically focusing on human stromal cells.
After trying various combinations of cells, Weinberg's lab finally succeeded in viewing carcinomas in the human tissue planted in the mice.
Cancer cell formation has proven to be very complicated -- so complex that Weinberg suggests that there may be no rationale behind it. However, his hope still is to eventually deduce a "small set of rules that govern all kinds of human cancer cell formation."
