Right or wrong?

Researchers at The University of Texas MD Anderson Cancer Center have discovered that two distinct types of cancer-associated fibroblasts (CAFs) accumulate in the pancreatic cancer microenvironment and play opposite roles, either promoting or inhibiting pancreatic cancer progression.

Results from preclinical studies suggest that targeting these unique CAF populations may offer strategies to improve the use of other treatments, such as chemotherapy and immunotherapy

"Cancer-associated fibroblasts are thought to regulate cancer progression, but targeting these cells in pancreatic cancer therapy often fails to improve patient outcomes and, in some cases, even causes Disease progression

Fibroblasts are cells in connective tissue that are involved in important biological processes, such as wound repair

The researchers then performed single-cell RNA sequencing to analyze gene expression and elucidate the types of CAFs present in pancreatic cancer

Interestingly, the researchers found that expression of these proteins in treatment-naïve human tumor samples correlated with patient outcomes

Using new mouse models, they then demonstrated that FAP+ and αSMA+ CAFs play diametrically opposite roles in the tumor microenvironment

In contrast, loss of αSMA+ fibroblasts resulted in more aggressive tumors and shorter overall survival, suggesting that these cells can slow pancreatic cancer progression

They found that the loss of FAP+ and αSMA+ CAF cells in the tumor caused changes in the expression of different genes, resulting in altered regulation of various cancer-related pathways and accumulation of different immune cells in the tumor microenvironment

To elucidate the different roles of FAP+ and αSMA+ cells, the team also analyzed secreted proteins that may affect tumors and surrounding cells

Corresponding author Raghu Kalluri, chair of the Department of Cancer Biology at MD Anderson Cancer Center, explained that these results suggest that these different types of cancer-associated fibroblasts are heterogeneous and play complex roles in cancer

"This new discovery helps move the field forward and sheds new light on the biological basis of pancreatic cancer and possible strategies for therapeutic intervention," Kalluri said

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Kathleen M.