Scientists working in the department of pathology and laboratory medicine at Weill Cornell Medicine have found that certain noncancerous cells may be useful for assessing prostate tumors and their potential to spread.
The team, led by Dr. Massimo Loda of Weill Cornell Medical College and the Sandra and Edward Meyer Cancer Center, focused on stromal cells. These are cells that do good work but may also show gene expression patterns that could play a role in prostate tumor growth and survival. To investigate the tumor microenvironment, the researchers used genetically engineered mouse models representative of prostate tumors at different stages of progression and human prostate tumor samples.
For the analysis, Loda's team generated a comprehensive single-cell RNA sequencing (scRNA-seq) compendium of the mouse prostate cancer mesenchyme. The work builds on previous research around a gene activity signature in prostate cancer stromal cells that appeared to encourage metastasis, according to the Weill Cornell news site, and could lead to prognostic tests on tumor-associated stromal cells that predict the aggressiveness of prostate tumors.
"This analysis contributes to the characterization of stromal cell subtypes with distinct expression profiles, which are likely regulated by key transcription factors orchestrating specific signaling pathways," the study's authors wrote in an article published January 8 in Nature Communications. "Our investigations also cover the interactions within mesenchymal cell populations and between mesenchymal and other cell types, such as epithelial or immune cells. The regulons and interaction networks we identify suggest additional roles of the PCa stroma in mediating interactions within the tumor microenvironment."
Combining single-cell RNA sequencing with artificial intelligence (AI)-based analytical methods, the researchers identified eight major subpopulations of tumor-associated stromal cells—in both mouse and human tumors—based on their distinct patterns of gene activity when a tumor is present.
"Strikingly, the researchers found that stromal cells surrounding prostate tumors often foster a molecular environment similar to bone, essentially preparing the tumor cells to spread to bones—a common site for prostate cancer metastasis," says Weill Cornell's article. "The analysis yielded lists of signaling proteins and networks that become abnormally active or inactive during these changes. These signaling interactions between tumor cells, stromal cells and immune cells might be targets for future prostate cancer treatments to block metastasis."
“If signs in the stromal cells point to the likely existence of a tumor, maybe an aggressive one, then perhaps you should biopsy again," Loda said.
