Imaging and isolation of prostate cancer circulating tumor cells.

摘要

Metastasis is the leading cause of death among prostate cancer patients, accounting for 99% of all deaths from the disease. Tumor cells shedding from primary and established metastases help the cancer invade distant sites within the body, furthering the metastatic disease. Luckily, these circulating tumor cells (CTCs) can provide a window to characterize the carcinoma population as a whole within an individual. The challenge lies in the concentration of these cells for study. The current CellSearch(c) technology has been able to demonstrate CTC capture in advanced stage prostate cancer, but lacks the ability to efficiently identify CTCs at the onset of disease. This deficiency is due to the targeting moiety having an affinity for a surface epitope that is shed from most cells as they enter circulation. The system also falls short, with the small quantities of cells that can be captured for further analysis. To overcome these challenges, a new target and better enrichment method are required. Adapting probes for an improved target such as prostate-specific membrane antigen (PSMA), a highly upregulated cancer-specific biomarker, is the first step in improving the approach for prostate CTC isolation. This can be achieved in two ways: either by direct labeling or pretargeting the cells and amplifying the signal with a secondary agent. This can be further improved by concentrating CTCs based upon their intrinsic differences from hematocytes, mainly density. Apheresis centrifugation techniques are not limited by blood volume, and do not target tumor cells through the use of biomarkers, but rather enable the adjustment of cell settling velocities to "skim" tumor cells out of whole blood. By employing these techniques together, a highly efficient CTC isolation process can be performed. More importantly, these techniques allow for larger cell populations to be screened, isolated, and cultured so that more information can be gained about the disease of a patient as a whole.