Researchers Find ‘Doorway’ That Allows Breast Cancer to Enter the Bloodstream

In In The News by Barbara Jacoby

By: Ann Pietrangelo


New research shows how breast cancer cells enter the bloodstream. The discovery could lead to combined therapies to stop some breast cancers from spreading.

Knowing if breast cancer is likely to spread could change the way we treat the disease.

It could also help some women avoid unnecessary treatment.

Breast cancer becomes life threatening when cancer cells break off from the primary tumor. Once cancer cells enter the bloodstream, they can travel to any part of the body.

Researchers at Albert Einstein Cancer Center and Montefiore Einstein Center for Cancer Care say they have found the “doorway” that allows breast cancer cells to enter the bloodstream.

The researchers used a mouse model of human breast cancer and mice implanted with human breast tissue. They also used real-time, high-resolution imaging.

The new study is published in Cancer Discovery.

How Breast Cancer Cells Enter the Bloodstream

In previous studies, Einstein-Montefiore researchers found that breast cancer spreads when three specific cells come into direct contact with each other.

One is a type of cell that lines the blood vessels (endothelial cell). Another is a type of immune cell found near blood vessels (perivascular macrophage).

The third is a tumor cell that creates a high level of the protein (Mena) that encourages cells to spread.

The tumor’s microenvironment of metastasis (TMEM) is the place where these three cells get together. It’s the doorway through which cancer cells enter the blood vessels.

Tumors with a high TMEM score are more likely to spread than tumors with lower scores.

Research shows that the TMEM macrophage releases vascular endothelial growth factor (VEGF). This protein increases blood vessel permeability. It’s a short-term effect, but it gives cancer cells ample opportunity to get through.

The researchers also found that transient blood vessel permeability and tumor cell entry into the blood stream happen at the same time. This only occurs at TMEM sites.

Using TMEM to Close the Doorway

According to the American Cancer Society, this year there will be about 231,840 new cases of invasive breast cancer in women.

About 40,290 women will die from it, mostly from metastatic breast cancer.

How we treat the disease could change in the not-too-distant future. This study opens the door to the development of new anti-metastasis therapies.

“This is a new paradigm. Once it catches on, it will change how oncologists make decisions,” said study leader John Condeelis, Ph.D., in an interview with Healthline.

Condeelis believes this information opens a whole new drug target. New drug combinations could mean the ability to convert a tumor from being potentially metastatic to being locally confined.

It’s a difference that could save lives.

Using Markers to Decide Treatment

According to Condeelis, in patients who have TMEM, current aggressive treatments can cause the primary tumor to rebound more aggressively after treatment ends. Using aggressive treatments blindly on all patients generates a sub-population that will experience more damage in the long run, he said.

Condeelis said clinical trials have shown an excellent predictive value of TMEM scores. Knowing a patient’s TMEM status will help in all stages of treatment.

And these markers may be used in general practice in the near future, said Condeelis. Information from a tissue biopsy would be scored for TMEM and would predict your chance of having a distant metastatic occurrence.

That would help guide doctors in deciding if more or less treatment is necessary.

Combined therapy with a drug that blocks TMEM function may protect against some of the adverse effects of chemotherapy.

Condeelis cautioned that clinical trials are needed to learn more about combined therapy.

The new research focused on the most common types of breast cancer. These findings may be helpful in other types of cancer research as well.

“The burden of proof is on us to confirm that TMEM is a common structure in all tumors derived from glands,” said Condeelis. “There’s a lot more work to be done.”