Cell Crosstalk: Scientists Discover Conversation Between Macrophages and Cancer Cells Which Potentiates Pancreatic Cancer Cachexia

Cachexia remains one of the major challenges for patients with cancer due to limited treatment options. Characterizing the connection between tumor cells and the immune microenvironment could help identify potential therapeutic targets for cancer cachexia.

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What is Cancer Cachexia?

Cancer cachexia is a wasting syndrome caused by a complex interaction of tumor and host factors. It is not a given condition with every cancer. In fact, it rarely occurs with breast cancer or brain cancer. This debilitating muscle-wasting condition almost always occurs in people diagnosed with pancreatic cancer.

As an understudied disease, cancer cachexia has no good treatments, nor does nutritional support help with the symptoms. Affected individuals lose their appetite and quickly lose weight, so they become weak and much less able to tolerate aggressive treatment for pancreatic cancer.

The combination of pancreatic cancer and cancer cachexia can diminish a person's quality of life. If there is a way to lessen the burden of cancer cachexia, patients can have a better prognosis in their battle against pancreatic cancer.

Cell Crosstalk

In a new research, scientists from the University of Oklahoma identified a previously unknown series of events which trigger the development of cancer cachexia. The study is a result of the collaboration with researchers from the University of Texas Health Science Center, Yale School of Medicine, and Johns Hopkins School of Medicine. The details of the research are discussed in the paper "The crosstalk between macrophages and cancer cells potentiates pancreatic cancer cachexia."

Led by Professor Min Li from the OU College of Medicine, the research team discovered the "crosstalk" between pancreatic cancer cells and macrophages. It serves as the first step toward the onset of cachexia. As a type of immune cell, macrophages usually protect the body from infection. In this case, however, the pancreatic cancer cells recruit them to do harm.

The conversation between these cells prompts increased secretion of tumor necrosis factor-like weak inducer of apoptosis (TWEAK). This protein is known to play an important role in cachexia by binding to receptors on the surface of muscle cells and causing inflammation. As a result, this sequence triggers the development of cachexia.

The result of this study helps provide evidence of an underlying mechanism of cachexia. The experts found that it is not the cancer cells alone or macrophages alone which start the process of cachexia, but the fact that they are talking to each other. As scientists understand how this condition begins, they can potentially develop a strategy to stop the cascade of events.

The research findings also provide a therapeutic window to intervene and potentially stop or reduce cachexia. This gives patients a better chance to fight pancreatic cancer. In the future, the experts plan to develop a drug which can possibly block the crosstalk between the cancer cells and macrophages.

Pancreatic cancer is difficult to detect in its early stages. More than 80% of patients with this condition are diagnosed when the cancer is in its advanced stage and treatment options are limited. Aside from providing a potential target for treatment, the team's research can also contribute to the ongoing study for a means of diagnosing pancreatic cancer in its earlier stage.