Cellular Environment Surrounding Cancer Cells: Friend or Foe?
The cells and tissues located adjacent to and within a tumor make up a unique “microenvironment,” which may play either a positive or negative role in cancer. Either way, scientists believe that the surrounding neighborhood has a powerful influence on how a tumor behaves—or whether cancer even develops in the first place.
Studying the microenvironment is a research pillar at the Wilmot Cancer Institute, and scientists are looking at it from every angle.
David Linehan, M.D., clinical director at Wilmot and a pancreatic cancer specialist, for example, is studying the role of the tumor microenvironment and the immune response to pancreas cancer. Linehan investigates a type of non-cancer cell known as tumor-associated macrophages (TAMs), which reside in the dense tissues surrounding pancreas tumors. He discovered that patients with high levels of TAMs are more likely to have a recurrence after surgery, and is investigating treatments that may block the mobilization of TAMs.
In addition to recent funding from the national Pancreatic Cancer Action Network (PANCAN), Linehan also was recently awarded a SPORE project through Washington University in St. Louis to continue his study of pancreatic cancer.
Another Wilmot researcher, Jacky Williams, Ph.D., a professor in Environmental Medicine and Radiation Oncology, studies how radiation treatment disrupts the microenvironment. Even when radiotherapy is aimed precisely at cancer cells, she explains, the environment of the surrounding normal cells can become chronically imbalanced. This might lead to serious treatment effects, such as fibrosis experienced by some patients following radiation therapy for lung cancer. It also might offer an explanation for second tumors that arise years after treatment ends.
“In the past, much of the focus of preventative measures for radiation has been on inflammation as the cause for the changes after therapy,” Williams says. “But we believe that when the normal microenvironment near cancer cells is disrupted, it might undergo a chronic remodeling that can cause treatment side effects and also create a comfortable place for a new cancer to develop.”
Williams recently received a large instrument grant from the National Institutes of Health, supporting a new, high-technology device enabling scientists to study models of lung, kidney, bone, prostate, and brain tumors, to learn exactly what happens in the microenvironment as cancer develops, during treatment, and when the tumor disappears or re-appears.
Wilmot is investing further in the new equipment, which is a type of tomotherapy (a delivery system for radiation), to study cancer’s interaction with the microenvironment more deeply.
Because the microenvironment is so complex, it’s difficult to untangle the positive and negative impact on cancer, says Laura Calvi, M.D., Dean’s Professor of Medicine, Wilmot investigator, and an endocrinologist.
Her interest is to focus on ways that the cells and tissues surrounding a tumor can be rallied to eliminate the cancer. For several years, for example, she has been studying the microenvironment in the context of blood cancers, which arise in the stem cells of the bone marrow. Her approach has been unique among blood cancer researchers, as she is looking for ways to target the bone marrow microenvironment to spur production of healthy blood cells.
“If we can activate those components that are normal and healthy to combat cancer,” she says, “we’ll have an additional tool.”
Williams and Calvi received a pilot grant from Wilmot, leveraging the new equipment, allowing them to gather preliminary data and apply for a larger award from the National Cancer Institute.
Lydia Fernandez |