Preclinical Study of Tumor Microenvironment in Bladder Cancer Offers Clues to Causes of Chemoresistance
Posted: Thursday, December 23, 2021
Tumor‐derived extracellular vesicles, contributors to the way that chemosensitive non-stem cancer cells and the tumor microenvironment communicate with each other, may provide a novel clue to why bladder cancer is associated with high rates of chemoresistance, according to Yi-Fen Lee, PhD, of the University of Rochester Medical Center in New York, and colleagues. The team used mouse model cell lines to learn more about how these vesicles—which are released by non‐stem cancer cells, an integral part of the cancer stem cell niche—may augment the aggressiveness of cancer stem cells in the tumor microenvironment.
Cancer stem cells can undergo self-renewal, tumorigenesis, and differentiation, the authors explained in Stem Cell Research & Therapy. As such, these cells are “often considered to be the driving force behind…acquisition of therapeutic resistance,” they continued. However, “the underlying mechanisms of [this] chemoresistance remain largely unknown.”
Dr. Lee and co-investigators conducted differential proteomic analyses to identify cargo protein candidates in the extracellular vesicles that were involved in mediating the communication between non‐stem cancer cells and cancer stem cells. Cargo proteins enriched in proteostasis‐related functions, they found, “significantly altered the development of cancer stem cells such that they were more intrinsically chemoresistant, aggressive, and better able to undergo self‐renewal.”
Functional studies will be necessary to confirm exactly how these extracellular vesicle cargo proteins maintain bladder cancer stem cell populations. This team’s data, however, “provide a valuable resource [for] future research efforts to better understand this novel mode of cell-cell communication that is critical for the survival, maintenance, and differentiation of cancer stem cells.”
Disclosure: The study authors reported no conflicts of interest.