A study published recently in PLOS ONE has reported on the discovery of the first reliable marker for the detection of carcinoma-associated fibroblasts (CAFs) in oral cancer tissues – PDGFRβ.
Until now, it has been difficult to study CAFs due to a lack of reliable markers for their isolation from tissue samples, despite the fact that researchers have demonstrated that they are strongly predictive of disease severity. It is hoped that more effective cancer therapies could now be created by combining existing tumor treatments with anti-PDGFRβ agents.
This study utilized a novel strategy for marker discovery, combining the use of gene expression datasets for bioinformatics analysis with the use of oral cancer specimens and cell lines for experimental assays.
The team from Baylor University School of Medicine (BUSM; TX, USA) first identified a set of collagen genes that they predicted would be CAF-specific: COL1A1, COL1A2 and COL3A1. They then used the Cancer Genome Atlas gene expression dataset, which contains hundreds of oral cancer samples, to look for other genes whose expression associated closely with the average expression of these three collagen genes. Through this process several markers were identified, including PDGFRβ, which they confirmed to be CAF-specific using immunostaining assays in oral cancer samples.
“Given the known association of CAFs with poor prognosis in certain cancers, including those of the head and neck, the identification of robust and reliable markers of these cells is necessary to further assess their role in tumor initiation and progression,” commented investigator Maria Trojanowska (BUSM).
“Identifying fibroblast markers has always been a challenge in the past, with one often having to resort to large-scale staining assays, with limited success. For the first time, we show how one can leverage large publicly available datasets to help prioritize these experiments, and help identify markers that are more robust and reliable,” explained Stefano Monti (Associate Professor of Medicine at BUSM).
The team hope that their research may help to identify mechanisms of action involved in the complex interplay between malignant and fibroblast cells, as well as aid in the discovery of new targets for cancer therapy.