NTP finds that arsenic encourages stem cells to become cancer-like
Working with arsenic and prostate cancer cells, researchers in the National Toxicology Program Laboratory found that cancer cells can trick stem cells into becoming cancer-like using extracellular vesicles, which are structures surrounded by membranes that are released by cells. The team isolated a type of extracellular vesicle called an exosome from cells previously transformed by arsenic exposure. These exosomes changed normal prostate stem cells to look and act like cancer stem cells. When the exosomes were removed, no transformation happened. Arsenic is a known human carcinogen that targets the prostate.
Cells inside tumors have long been known to communicate with each other using secreted vesicles containing oncogenic factors, such as proteins and RNA, to recruit surrounding cells. The researchers demonstrated that the extracellular vesicles secreted by arsenic-transformed cells contained significantly higher amounts of mRNA for a host of oncogenes, genes that resist cell death, and inflammation-related genes. In addition, they found arsenic exposure changed the overall number of microRNAs loaded into exosomes. Further investigation of the oncogene KRAS concluded that exosomal KRAS plays a role in recruiting normal stem cells to function in the tumor environment following arsenic exposure. However, the scientists stress that more work remains to identify other factors involved in the transformation process. (GK)
Citation: Ngalame NNO, Luz AL, Makia N, Tokar EJ. 2018. Arsenic alters exosome quantity and cargo to mediate stem cell recruitment into a cancer stem cell-like phenotype. Toxicol Sci 165(1):40–49.