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Stromal cells could also be useful in assessing prostate tumors’ potential to spread

Non-cancerous cells called stromal cells, that are present in and around prostate tumors, could also be useful in assessing these tumors’ potential to spread, and will even be targets for future prostate cancer treatments, based on a study led by researchers at Weill Cornell Medicine.

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

Within the study, published Jan. 8 in Nature Communications, the researchers performed essentially the most comprehensive evaluation up to now of stromal cells in and around prostate tumors. Examining prostate tumor mouse models in addition to 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’ evaluation also uncovered signaling interactions amongst stromal cells, tumor cells and nearby immune cells that provide potential targets for stopping metastasis.

These results illuminate the substantial impact of stromal cells on prostate cancer progression, and point to the potential for recent prognostic and therapeutic strategies,” said study senior creator Dr. Massimo Loda, chairman 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.

The study’s co-first authors were Dr. Hubert Pakula, Dr. Mohamed Omar and Ryan Carelli, scientists working within the Department of Pathology and Laboratory Medicine on the time of the study. Dr. Omar is now an assistant professor of research in pathology and laboratory medicine.

The emerging importance of tumor microenvironment cells

Tumor progression is driven not only by the acquisition of recent mutations in cancerous cells, but in addition by tumor-induced—and tumor-supporting—changes in non-cancerous cells.

Thus far, a lot of the research on these “tumor microenvironment” cells has focused on immune cells, which might be co-opted to suppress natural anticancer immunity and block the results of cancer immunotherapies. However the tumor-supporting activities of stromal cells has also caught the eye of scientists. In 2017, for instance, Dr. Loda’s team discovered a gene activity signature in prostate cancer stromal cells that appears to encourage metastasis, and will be useful in predicting the spread of tumor cells which is the explanation for most cancer mortality.

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

Combining a complicated technique called single-cell RNA sequencing with AI-based analytical methods, the researchers identified eight major subpopulations of tumor-associated stromal cells—in each mouse and human tumors—based on their distinct patterns of gene activity when a tumor is present.

They showed that a few of these tumor-associated patterns change when the cells acquire recent cancer-driving mutations, and as tumors grow to be metastatic. Strikingly, the researchers found that stromal cells surrounding prostate tumors often foster a molecular environment much like bone, essentially preparing the tumor cells to spread to bones—a standard site for prostate cancer metastasis.

The evaluation yielded lists of signaling proteins and networks that grow to be abnormally energetic or inactive during these changes. These signaling interactions between tumor cells, stromal cells and immune cells is perhaps targets for future prostate cancer treatments to dam metastasis, Dr. Loda noted.

Along with searching for recent therapeutic targets, Dr. Loda and his team hope to make use of their data and recent experiments to develop prognostic tests on tumor-associated stromal cells that predict the aggressiveness of prostate tumors—which in turn could help physicians make higher treatment decisions.

“One could even imagine using such a test on biopsy samples where no tumor tissue is found,” said Dr. Loda, who can be a member of Weill Cornell Medicine’s Sandra and Edward Meyer Cancer Center. “If signs within the stromal cells point to the likely existence of a tumor, perhaps an aggressive one, then perhaps you must biopsy again.”


Journal reference:

Pakula, H., et al. (2024). Distinct mesenchymal cell states mediate prostate cancer progression. Nature Communications.

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