Researchers at the Tufts University School of Medicine (TUSM), the Sackler School of Graduate Biomedical Sciences at Tufts and Tufts Medical Center (TMC) have recently discovered the cell of origin for a common type of breast cancer.
Co-primary investigators Dr. Charlotte Kuperwasser, associate professor at TUSM, and Dr. Philip Hinds, deputy director of TMC Cancer Center and professor at TMC, authored the study, which was published Jan. 19 in the Cancer Cell journal.
The Tufts research team conducted an in-vivo study that identified specific varieties of breast stem and progenitor cells, something that up until now has been difficult for scientists to do, according to a press release from TUSM and Sackler.
According to the study, the two known types of breast cancer originate from different progenitor cells.
The most common form of breast cancer, luminal-like cancer, is sensitive to hormones and grows relatively slowly. In comparison, the other form, basal-like cancer, lacks sensitivity to hormones and is more aggressive.
Hinds explained that the study found that the former originates from one type of progenitor cell, lobule progenitors, which are the self-renewing cells required to generate the milk-producing structures in breast tissue during pregnancy and lactation.
"We discovered that this population of progenitor cells depends on the activity of a protein called Cyclin D1 for self-renewal and differentiation," Hinds said. "Inhibiting Cyclin D1 prevented the formation of breast tumors in mice."
Kuperwasser said that the experiments performed included mating a tumor-prone mouse with a non-tumor-prone mouse.
"There was something wrong with the tissues in the first-generation mice, and when we tested the mice with pregnancy and lactation, the problem became more and more apparent," Kuperwasser said. "We wondered if it was a problem in development that might be linked to a fixed cell origin that was linked with the origin of cancer."
Hinds said that although cancer researchers have known for many years that a particular transgenic mouse causes breast cancer, the results of the recent study affirm that the cancer does not necessarily lead to the expansion of tumors.
"What has become increasingly clear is that not every type of epithelial cell is able to develop into a tumor, and that only specific cell types in the mammary gland eventually can become tumors," he said.
The discovery, according to Hinds, confirms a widely accepted idea that specific origin cells exist. In addition, it has revealed to the researchers that they can target "kinase enzymatic activity," which is largely effective on certain types of cancer.
Kuperwasser is optimistic that the research will be able to be applied soon, as drugs already targeting the specific enzyme are in clinical trials to treat other diseases.
"It would be useful to expand the trials to breast cancer," Kuperwasser said. "What is unclear is whether this will be effective or not."
Hinds indicated that understanding the enzyme is very translatable into the design of a clinical trial in the near future.
"The next step is to either use mouse models with these compounds, or if the drug targeting the enzyme is approved, go into clinical trials and subdivide the patients into groups that would represent that results that we predict," Hinds said.
Based off of its new findings that inhibition of Cyclin D1 prevents mammary tumor formation, Hinds said his research team would like to next investigate whether that inhibition can also slow or reverse the growth of existing tumors.
"We predict that targeting Cyclin D1 would diminish the progenitor cells that drive luminal-like tumor growth," Hinds said.
