In science, improving research methods is the kind of unglamorous work that can have a hard time finding takers, both among researchers and granting agencies. But a paper in the Aug 13, 2007 issue of Cancer Cell rather spectacularly shows the sorts of payoff it can have. By developing a new culture medium, researchers at MIT's Whitehead Institute for Biomedical Research, Harvard Medical School, and the Dana-Farber Cancer Institute were able to culture new types of breast epithelial cells, and develop a rich source of cancer stem cells as well as gain insight into the determinants of metastasis.

Tissues are made up of many different cell types, and which of those types are used in research depends partly on how easy, or even possible, it is to culture them. But what easily cultured cells do in the petri dish "doesn't necessarily have anything to do with real cancer," Whitehead member and senior author Robert Weinberg told BioWorld Today.

Specifically, the standard medium for culturing breast cancer cells favors the growth of a specific cell type, so-called human mammary epithelial cells. These cells tend to form a certain type of breast tumor that is clinically rare. The majority breast cancers are adenocarcinomas, which are a very different beast.

Developing a culture medium that would support the growth of cells that can form adenocarcinomas, Weinberg said, was "totally Tan Ince's work — he realized that current media were inadequate" for the job. "All the credit goes to Tan," he said the first author of the paper.

Ince developed a chemically defined medium that favored the growth of a different type of breast cell, which the scientists refer to as breast primary epithelial cells.

Using their culture system, the researchers were able to show that a cancer cell is not a blank slate whose metastatic potential is determined by the mutations it acquires. When the researchers transformed both cell types with identical cancer-causing mutations, the cells showed very different metastatic potential. Injecting the same amount of either cell type into mice led to primary tumors of about the same size. But almost all of the mice injected with breast primary epithelial cells had metastases, while none of the mice injected with human mammary epithelial cells did.

Weinberg said the finding that different types of cells appear to have different predilection to metastasize when they acquire the same mutations "ultimately could be the most important take-home lesson of the paper." Current research focuses on the sorts of mutations that make a cancer cell more or less likely to metastasize. But the work published in Cancer Cell suggests, somewhat ominously, that "the die may be cast at the very beginning."

Another benefit of the new medium is that it supports the growth of cancer stem cells much more effectively than current media. When the scientists injected mice with breast primary epithelial cells, as few as 100 transformed breast primary epithelial cells were necessary to seed tumors in the animals, suggesting that there is a high proportion of cancer stem cells among them. It takes an injection of at least a million transformed human mammary epithelial cells to see tumors in mice.

"This work could provide a boon to researchers who study these elusive cancer stem cells by offering a bountiful source of them," Weinberg said.

Weinberg said that although the new medium "is a big step forward," it is probably not the final step. It is logical to think that either further refining this medium or developing new ones altogether will allow the culturing of yet more cell types, which will in turn open up new areas for scientific study.

And though the new medium has definitely proven its usefulness, that does not mean it has yielded all its secrets. When asked whether it is clear why breast primary epithelial cells grow better in the new medium, Weinberg was succinct: "In a word, no."