Stromal cells may help predict prostate cancer metastasis

Non-cancerous cells called stromal cells, found in and around prostate tumors, may be useful in assessing the potential for these tumors to spread and may even be possible, according to a study led by Weill Cornell researchers. targets for future treatments against prostate cancer. Medicine.

Stromal cells, present in all organs, contribute to wound healing, blood vessel formation and structural support of tissues. Scientists know that tumors often co-opt stromal cells to create a molecular environment more favorable for tumor growth and survival. But their precise roles in different cancers are only beginning to be delineated.

In the study, published January 8 in Natural communications, researchers performed the most comprehensive analysis to date of stromal cells in and around prostate tumors. By examining mouse models of prostate tumors as well as samples from human patients, they identified eight subpopulations of stromal cells with distinct tumor-associated patterns of gene activity. They found that certain changes in these patterns predicted tumor spread or metastasis.

The researchers’ analysis also revealed signaling interactions between stromal cells, tumor cells and neighboring immune cells that offer potential targets for preventing metastasis.

“These results highlight the substantial impact of stromal cells on the progression of prostate cancer and suggest the possibility of new prognostic and therapeutic strategies,” said Dr. Massimo Loda, lead author of the study, president of the Department of Pathology and Laboratory Medicine and the David D. Thompson Professor of Pathology at Weill Cornell Medicine and Pathologist-in-Chief at NewYork-Presbyterian/Weill Cornell Medical Center.

Co-first authors of the study were Hubert Pakula, Mohamed Omar and Ryan Carelli, scientists working in the Department of Pathology and Laboratory Medicine at the time of the study. Omar is now a research assistant professor of pathology and laboratory medicine.

Tumor progression is driven not only by the acquisition of new mutations in cancer cells, but also by tumor-induced – and tumor-sustaining – changes in non-cancerous cells.

Until now, most research on these “tumor microenvironment” cells has focused on immune cells, which can be harvested to suppress natural cancer immunity and block the effects of cancer immunotherapies. But the activities of stromal cells that support tumors have also attracted scientists’ attention. In 2017, for example, Loda’s team discovered a gene activity signature in prostate cancer stromal cells that appears to promote metastasis and could be useful in predicting the spread of tumor cells, which are at the cause of most cancer deaths.

In the new study, the team performed a comprehensive analysis of stromal cells in prostate cancer, using representative mouse models of prostate tumors at different stages of progression and human prostate tumor samples.

By combining an advanced technique called single-cell RNA sequencing with AI-based analytical methods, researchers identified eight major subpopulations of tumor-associated stromal cells (in both mouse and human tumors) based on their distinct patterns of genetic activity when a tumor is present. .

They showed that some of these tumor-associated patterns change when cells acquire new cancer-causing mutations and when tumors become metastatic. Surprisingly, researchers have found that the stromal cells surrounding prostate tumors often promote a molecular environment similar to that of bone, essentially preparing the tumor cells to spread to bone, a common site for prostate cancer metastasis.

The analysis yielded lists of proteins and signaling networks that become abnormally active or inactive during these changes. These signaling interactions between tumor cells, stromal cells and immune cells could be targets for future prostate cancer treatments to block metastasis, Loda noted.

In addition to searching for new therapeutic targets, Loda and his team hope to use their data and new experiments to develop prognostic tests for tumor-associated stromal cells that predict the aggressiveness of prostate tumors, which could help doctors to make better treatment choices.

“One could even imagine using such a test on biopsy samples where no tumor tissue is found,” said Loda, who is also a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. “If there are signs in the stromal cells that indicate the likely existence of a tumor, perhaps an aggressive one, then you may want to do a new biopsy.”