A recent study led by researchers at Weill Cornell Medicine reveals that stromal cells, non-cancerous cells found in and around prostate tumors, may play a crucial role in assessing the tumors’ potential to spread. The study, published in Nature Communications, marks the most comprehensive analysis of stromal cells in prostate tumors to date.
Stromal cells, present in all organs, are known for their contribution to wound healing, blood vessel formation, and structural support for tissues. In the context of tumors, these cells are often co-opted to create a more supportive environment for tumor growth.Â
The researchers utilized prostate tumor mouse models and samples from human patients to identify eight subpopulations of stromal cells with distinct patterns of gene activity associated with tumors. The study found that specific changes in these patterns could predict the spread, or metastasis, of tumors. The analysis also revealed signaling interactions among stromal cells, tumor cells, and nearby immune cells, offering potential targets for preventing metastasis.Â
Dr. Massimo Loda, the senior author of the study and chair of the Department of Pathology and Laboratory Medicine at Weill Cornell Medicine, emphasized the impact of stromal cells on prostate cancer progression. The findings open up possibilities for new prognostic and therapeutic strategies.Â
The study focused on the tumor microenvironment, exploring the role of non-cancerous cells, particularly stromal cells, in driving tumor progression. While previous research has primarily concentrated on immune cells within the tumor microenvironment, this study sheds light on the tumor-supporting activities of stromal cells. In a 2017 study, Dr. Loda’s team identified a gene activity signature in prostate cancer stromal cells that appeared to encourage metastasis.Â
The recent study utilized advanced techniques, including single-cell RNA sequencing and artificial intelligence (AI)-based analytical methods, to identify subpopulations of tumor-associated stromal cells based on their distinct gene activity patterns. The researchers observed changes in these patterns as tumors acquired new cancer-driving mutations and progressed to a metastatic state. Notably, stromal cells surrounding prostate tumors were found to create a molecular environment resembling bone, potentially preparing the tumor cells for metastasis to bones, a common site for prostate cancer metastasis.Â
The analysis uncovered signaling proteins and networks that became abnormally active or inactive during these changes. These signaling interactions between tumor cells, stromal cells, and immune cells could be potential targets for future prostate cancer treatments to block metastasis.Â
In addition to identifying therapeutic targets, the researchers aim to use their data to develop prognostic tests based on tumor-associated stromal cells. Such tests could predict the aggressiveness of prostate tumors, aiding physicians in making better treatment decisions.
Dr. Loda suggested the potential use of such a test on biopsy samples where no tumor tissue is found. If signs in the stromal cells indicate the likely existence of a tumor, especially an aggressive one, a rebiopsy could be considered.Â
This groundbreaking research not only enhances our understanding of the role played by stromal cells in prostate cancer but also holds promise for the development of targeted therapies and prognostic tools. The study’s findings may contribute to more personalized and effective approaches in the diagnosis and treatment of prostate cancer.Â
Journal Reference Â
Hubert Pakula et al, Distinct mesenchymal cell states mediate prostate cancer progression, Nature Communications (2024). DOI: 10.1038/s41467-023-44210-1.Â
