The discovery of a specific gene expression profile of prostate cancer could herald in new treatments in future, scientists from the YCR Cancer Research Unit at the University of York and Pro-cure Therapeutics Ltd have said.
The scientists have uncovered 581 genes that are differentially expressed in some prostate cancer cells, highlighting several pathways vital to cancer stem-cells biology, and offering targets for new chemopreventative and chemotherapeutic approaches.
AdvertisementThese cells correspond to less than 0.1 percent of prostate cancer tumors, with properties that makes them stand out as cancer stem cells, like self-renewal, high invasiveness, longer lifetime than normal stem cells. They also feature a primitive epithelial phenotype and can differentiate to recapitulate phenotypes seen in prostate tumors. The cells are found in all stages and types of prostate cancer.
Usually, expression profiling of prostate cancers makes use of tumor cell mass samples for identifying individual genes. However, in the current study, researchers utilised advances in microarray and target labelling technologies for coming up with a functionally annotated expression profile of these prostate cancer stem cells.
The researchers created a malignant stem cell signature by combining genes significantly overexpressed in stem cells with those significantly overexpressed in malignant stem cells. Quantitative RT-PCR, flow cytometry and immunocytochemistry were used to confirm the gene expression changes.
It was found that genes linked with inflammation were prominent in the cancer stem cell expression profile. Potential therapeutic target NF?B is known to promote cell survival.
It was demonstrated that an NF?B inhibitor initiated programmed cell death in cancer stem cells, but spared normal stem cells. This offered a potential therapeutic target for this rare group of cells, unlikely to be affected by current chemotherapy regimens.
"For the first time we are looking at the subpopulation of cancer cells which actually initiate new tumors. The genetic profiling we have carried out should stimulate new lines of research directed towards stem cell treatments for cancer," explained Anne Collins, who coordinated the study.
The findings of the study are published in BioMed Central's open access journal Genome Biology.
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