Dr. Irene Bertolini of the Altieri Lab investigates extracellular vesicles and their role in metastasis
When cancer spreads, cancer kills. Cancer’s ability to spread to other parts of the body — a process known as metastasis — makes the disease dangerous and more complicated both for the patient and the medical professionals treating the disease. Decades’ worth of cancer research has investigated the multitude of factors that can drive metastasis.
One of these factors is the presence of extracellular vesicles, or EVs, the research interest of Irene Bertolini., Ph.D., an associate staff scientist in Wistar’s Altieri Lab. Her research shows that EVs from cancer cells can contribute to the conditions that allow cancer to flourish and spread in breast cancer, the second most common cancer in women.
Vesicles are small particles created by cells that contain biological materials. When a vesicle leaves a cell, that vesicle is said to be extra-cellular. Cancerous cells emit EVs just like regular cells, but, being cancerous in origin, breast cancer EVs can carry carcinogenic properties.
Dr. Bertolini investigates the connection between breast cancer EVs and the tumor microenvironment, which can be thought of as the biological garden that cancer grows in. Like garden plants, cancers grow and spread better in certain conditions. Cancer cells work to foster those conditions, and Dr. Bertolini found that EVs produced by hypoxic (oxygen-deficient) breast cancer cells promote a variety of carcinogenic and metastatic conditions.
Using EVs from hypoxic breast cancer cells, Dr. Bertolini found that EVs increase angiogenesis, the process that forms new blood vessels. When new blood vessels form around cancer, the cancer cells use them to siphon more of the body’s nutrients, which allows cancer to grow and potentially metastasize.
Dr. Bertolini’s research also revealed that the EVs showed increased packaging of a protein called HIF1α, which has been linked to a variety of metastatic cancers. And relative to controls, tumor formation & growth in mice treated with cancer-derived EVs was significantly more rapid.
“EVs from cancerous cells basically transmit packets of potent cancer-causing material,” said Bertolini. “Where EVs move, conditions conducive to cancer follow.” Because EVs can move beyond cancerous cells and into healthy tissue, she says, they have the capacity to drive metastasis.
To that end, Dr. Bertolini plans to study the role of hypoxic breast cancer EVs in metastasizing to the liver, specifically. So far, she has found that EVs do indeed migrate to the liver, where she’s observed pro-cancer effects like increased angiogenesis and reduced counts in anti-tumor T-cells.
“Understanding why EVs help cancer spread is the first step in understanding how to stop them,” said Dr. Bertolini. “If we know what they do and how they do it, that’s half the battle.”