researchers from University of Texas MD Anderson Cancer Center Published new findings on how pancreatic cancer cells grow and protect themselves.The study was published Thursday in cancer cellsrevealing that cancer cells make their own unique form of collagen.
The collagen produced by cancer cells is fundamentally different from the normal collagen produced by the body. Raghu Kalluri, Ph.D., one of the authors of the study, said this means that drug developers may have a new, highly specific therapeutic target.
Dr. Kalluri and his research team set out to better understand the changes pancreatic cancer cells undergo to help them grow and proliferate. They found that a key reason these cancer cells grow so rapidly is that they produce an abnormal form of collagen that cannot be found elsewhere in the body.
Normal collagen is a heterotrimeric protein. This means two α1 (α1) chains and one α2 (α2) chain Assemble to form triple helical structures as part of the extracellular matrix. Cancer cells produce collagen differently because it only expresses the alpha1 gene.Therefore, its extracellular matrix is homotrimer It consists of three α1 chains. This unique extracellular matrix protects cancer cells by repelling T cells, helping the cancer survive and multiply.
“It’s a unique collagen that appears to form a barrier or protective layer around cancer cells,” explains Kalluri. “It doesn’t allow the immune system to see cancer cells, and it can’t kill them.”
To further understand their findings, Kalluri and his team created a knockout mouse model of pancreatic cancer, That means they genetically modified cancer cells and implanted them in mice. They removed homotrimers from cancer-specific collagen and found that this reduced cancer cell proliferation and immunosuppression in mice.
In addition, the researchers found that deletion of homotrimers reprogrammed the tumor microbiome in mice. Loss of cancer-specific collagen results in changes in tumor bacterial composition, as well as a decrease in myeloid-derived suppressor cells and an increase in T cells. This was reversed when antibiotics were introduced, meaning that cancer-specific collagen could support cancer growth by strengthening the tumor-friendly microbiota.
While the study only examined pancreatic cancer, collagen homotrimers are also present in other types of cancer, including lung and colon cancers, Kalluri said. That could mean a wide range of opportunities to innovate cancer treatments, he said.
“It’s a whole new target,” he said. “This new target of cancer cells on their surface could make them live longer and happier. By targeting and blocking it with drugs, we can test a whole new way of treatment.”
The discovery of cancer-specific collagen opens the door for researchers to create drugs that can target and attack homotrimers to kill cancer cells. Kalluri said his team will continue their research to learn more about cancer-specific collagen so that drug developers can gain more information in their efforts to eventually develop novel tumor therapies.
“This presents a huge opportunity for biopharmaceutical companies,” he said. “This work will be of great interest to the pharmaceutical industry and investors.”
Image credit: National Cancer Institute
