In a new study, researchers have identified a series of molecular interactions that may be key to stopping the spread of cancer cells. The new study identifies, for the first time, a link between two important groups of molecules that regulate intercellular communication within tumors to increase cancer cell migration and metastasis.
In a new study, researchers from the Medical University of South Carolina have identified a series of molecular interactions that may be key to stopping the spread of cancer cells. Currently, there are no reliable treatments to prevent metastasis, the leading cause of death in solid cancer tumors. This new study identifies for the first time a link between two important groups of molecules that regulate intercellular communication within tumors to increase cancer cell migration and metastasis. The findings were recently published in the journal Cell Reports in a paper titled “Crosstalk between pro-survival sphingolipid metabolism and complement signaling induces inflammasome-mediated tumor metastasis.”
The complexity of cancer poses many challenges for scientists, oncologists, and patients. “Cancer is not a single cell, a single protein, or a single treatment for a disease but a complex process, which is why there is still so much we don’t understand,” said Dr. Besim Ogretmen, author of the paper, who is from the Medical University of South Carolina, “and cancer metastasis causes about 90 percent of cancer deaths, and the challenge is that we still don’t understand the biological mechanisms that lead to metastasis.”
In order to develop novel therapeutic approaches for cancer, the Ogretmen lab is studying how sphingosine, a class of lipid molecules, functions in cancer cells. Sphingosine-1-phosphate (S1P) is the key lipid in most sphingosine chemistries. As an expert in sphingolipid biology, Ogretmen has published several studies that confirm the function of S1P in cancer development and progression.
The idea for this novel discovery was developed by Ogretmen during a casual brainstorming session with colleague Carl Atkinson. “Sphingolipid signaling and complement signaling have similarities in that both play a role in cancer, and we asked each other if we could see if there was a conversation between sphingolipid signaling and complement signaling, but we didn’t find anything in the existing literature in that regard,” said Ogretmen, “which led us to start this project to find answers to these questions.”
The complement system is part of the immune system that destroys pathogens and aids the healing process after an injury or infection. However, studies conducted over the past five years have revealed that some tumors can activate the complement system to improve tumor cell survival and metastasis.
Understanding the back-and-forth communication between different biological systems, not just individual molecules, is the future direction of research to understand cancer and improve therapies because the different biological systems in the body are intertwined. The Ogretmen team, in close collaboration with Atkinson and Stephen Tomlinson, PhD, a researcher at the Medical University of South Carolina Hollins Cancer Center, aims to understand how two key systems—S1P and complement—are linked and how they coordinate cancer metastasis. Although most scientists study a single cancer type, this new study is unique in that its findings apply to many types of solid tumors.
Through a series of elegant experiments, Ogretmen’s team has demonstrated a new biological mechanism that regulates how cancer cells talk to each other before they produce more aggressive cancers. High levels of S1P in cancer cells activate a complement molecule called C3, leading to the formation of a pro-inflammatory complex called the inflammasome. This cascade of events and inflammasome activity drives the spread of cancer cells.
This new study has discovered that C3 molecules can be activated in cancer cells. “This new study is very significant in terms of what can be learned from it in the future,” added Ogretmen, “and we revealed new combinations and introduced new concepts for new therapy development.”