Cancer stem cells present in testicular germ cell tumors (TGCTs) have been shown to provide increased chemosensitivity to these tumors compared to other types of cancers. The science supporting this finding has been explained in a recent study published in Cell Reports. Understanding the factors that contribute to this chemosensitivity could help identify treatments for other cancers.
"The study provides new insights into the basis for the responsiveness of testicular cancer to chemotherapy, which has always been an intriguing observation, but the basis for it was not clear," said Robert Weiss, professor of biomedical sciences at Cornell's College of Veterinary Medicine and senior author of the study.
A genetically engineered TGCT mouse model was developed that mimicked malignant TGCTs in men. The model was designed to conditionally activate Kras oncogene and inactivate the Pten tumor suppressor gene in pre-meiotic germ cells which resulted in the development of testicular germ cell tumors. Embryonic carcinoma (EC) cells made up a large population of the tumors. Using immunohistochemistry (IHC), the team determined that these cells were cancer stem cells (CSCs) due to their expression of OCT4, an important pluripotency marker. The CSC population was shown to be mostly depleted following DNA-damaging chemotherapy, emphasizing that CSC chemosensitivity is a significant factor in the overall responsiveness of TGCTs to chemo treatments.
Image: A low magnification image of a germ cell tumor, called a teratocarcinoma, from a new mouse model developed to study testicular cancer. A cluster of cancer stem cells, termed embryonal carcinoma, is shown at higher magnifiation at the bottom. Image curtosy of Tim Pierpont, Cornell University.