Reevaluating the Nature of Hemangiosarcoma

04/24/2015

Hemangiosarcoma is a type of cancer that is quite common in dogs. It is aggressive and deadly; more than 50% of dogs with hemangiosarcoma die within four to six months of diagnosis. Treatment is difficult, in part because the origin of hemangiosarcoma is poorly understood. That’s why it’s so exciting that two studies from researchers at the University of Minnesota, Twin Cities have begun to shed new light on where these tumors come from and how they grow.

Hemangiosarcoma tumors are remarkably diverse. They can occur in almost any organ, although, in dogs, they are most commonly located in the spleen, the right auricle of the heart, and the skin.  They are also quite variable in configuration. Hemangiosarcoma tumors contain intricate networks of blood vessels, but under the microscope they can appear as solid dense masses or they can contain large channels or pools of blood. The diversity of hemangiosarcoma and the poor responses to conventional treatments and to treatments targeting blood vessel formation have made scientists question previous assumptions about the origins of this disease. The goal is that understanding what type, or types, of cells give rise to this cancer, and how these cells interact with tissues where the tumors grow could potentially lead to better ways to treat the disease –  or even a way to keep them from forming in the first place.

When Drs. Jaime Modiano, Erin Dickerson, and their colleagues began trying to classify the types of hemangiosarcoma found in dogs, they discovered something quite interesting. The tumors could be broken down into three distinct types – one with markers associated with blood vessel growth, another with markers associated with inflammation, and a third with markers associated with fat metabolism. They first thought that the tumors came from different origins, but several pieces of evidence worked against that conclusion. First, several dogs had multiple tumors of different types, which implied that they might all spring from the same, problematic ancestor cell. Second, when the scientists grew tumor cells in the lab, they found that they could get a single cell to differentiate into any one of the three types of tumor. That suggested that all three types of hemangiosarcoma tumor might actually derive from a single type of multipotent cell, presumably a stem cell from the bone or fatty tissue, and that tumors develop different structures and characteristics based on the signals present in the environments where they embed and mature.

The logical next steps from these findings were to study how hemangiosarcoma tumors influenced the processes of inflammation, blood vessel growth, and fat metabolism in their local environment. One molecule that seemed to play an important role in those negotiations was the inflammatory cytokine interleukin 8 (IL-8). Dr. Modiano’s group showed that blocking IL-8 made it more difficult for tumors to become established in the body, which strongly suggests that the molecule plays an important role in establishing communication between the tumor and the surrounding environment. Ongoing work seeks to confirm and expand these results to achieve the goals of developing effective strategies to diagnose, treat, and eventually prevent hemangiosarcoma in dogs.

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