A study has found that breast cancer cells are highly mobile even in the early stages of breast cancer. The study conducted at the Salk Institute for Biological Studies have discovered that this might trigger the recurrence of tumors in the same breast by traveling through the milk ducts.
The study suggested that these cells, although not yet invasive, could stray off along milk ducts and seed new tumors within the same breast.
The presence of these highly motile cells may have implications in the treatment decisions in future, the researchers said.
The study was led by Gray Pearson, Ph.D, a postdoctoral researcher in the Molecular and Cell Biology Laboratory at the Salk.
"A lack of invasion suggested a lack of motility. But that's not so," said Pearson.
"This is an exciting finding because it suggests that cells might acquire migratory properties much earlier than expected," said senior author Tony Hunter, Ph.D., a professor in the Molecular and Cell Biology Laboratory.
The researchers said that the early stage cancer usually arises in a duct, containing cells that are non-invasive and can be easily detected, owing to new screening mechanisms. These tumors arising in the duct are called DCIS (ductal carcinoma in situ).
However, the cancer cells in this duct do not spread to the surrounding tissues at this stage.
For the study, the researchers recreated the duct of the mammary gland using a tissue culture model. Then, human cells isolated from breast tissue were implanted in a 3-D matrix that was similar to their natural surroundings.
Instantly, these cells developed into hollow structures called acini, resembling tiny milk ducts.
Then they triggered the ERK1/2 MAP kinase pathway, a signaling cascade frequently activated during the development of tumors, and examined how breast cancer cells learned to walk, in real time.
"We quickly realized that there was a significant cell movement, which was quite surprising. Within 24 hours, a large number of these spheres had lost their organization, and the cells started to dance around," said Pearson.
However, highly invasive cells could easily pass through the basement membrane towards the surrounding tissue but the motile cells still could not cross the boundaries of the ERK-activated acini.
"But the acquisition of motility prior to invasion presumably lowers the barrier for future invasive growth," explained Pearson.
"The advent of live-cell imaging allows us to watch labeled cells move around in tissues and learn a lot about their behavior, which wouldn't be revealed in cultured cells," said Hunter.
Though lumpectomy (surgical removal of the tumor and surrounding tissue) is the treatment that is followed usually to treat DCIS, there was an increasing rate of recurrent breast cancer growth in DCIS patients after surgery.
Hence, the oncologists thought of adding gamma radiation after surgery to control wandering tumor cells and cut the risk of recurrent breast cancer. However, this decision is entirely dependent on the size of the tumor, the authors said.
"Our findings suggest that, if a DCIS contains these highly motile cells, the patient may have an increased risk for recurrent growth. Under these circumstances you would consider adding radiation treatment regardless of tumor size," said Pearson.
The study was published in the recent issue of the Journal of Cell Biology.