Functional Characterization of Circulating Tumor Cells

We recently published a paper in PLoS One (go here) about functional characterization of prostate circulating tumor cells.  This work was the product of many people’s efforts, including Erica, Jason, Jim, and Steven in our group–Erica did chip design and fab and SOP development, Jason did initial surface chemistry characterization and capture experiments, Jim did CFD analysis, and Steven characterized prostate cell adhesion parameters.

The point of this paper was to show that we can capture prostate circulating tumor cells by use of a prostate-specific (rather than pan-epithelial) antibody–this is important because the antibodies to epithelial markers (e.g., EpCAM) may suffer when cells undergo epithelial-to-mesenchymal transition as part of the metastatic process.  Also, we showed that we can characterize cells functionally, meaning that we see how the living cells

A circulating prostate cancer cell stained to show the nucleus (upper left), tubulin (upper right), and PSMA (lower left). The bundled tubulin seen at upper right is indicative of drug-target engagement when taxane chemotherapy is used.

respond to their environment, in contrast to the (much more common) enumeration of cells or characterization of genetic material.

We are now looking forward to applying these techniques in clinical trials, with the hopes of proving that functional characterization on microdevices is a better way of predicting which patient should be on which chemotherapy regimen.

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New grant to study pancreatic cancer

We recently got NIH approval for a new grant to study pancreatic cancer. This work involves using our GEDI device on the blood of pancreatic cancer patients to try to learn about how pancreatic cancer spreads during early disease.

Pancreatic cancer is the fourth leading cause of death due to cancer in the United States, killing an estimated 35,000 people in 2009. The 5-year survival rate for patients diagnosed with pancreatic cancer is very low–5% or so. A primary driver of this is that close to 80% of patients with pancreatic cancer have metastatic disease upon diagnosis. Almost all patients eventually develop disseminated metastatic disease as a cause of death. This suggests that pancreatic cancer spreads early, and small metastases spread before pancreatic tumors can be detected with current techniques and removed. We hope that we can learn about this process by detecting pancreatic cells in the blood of cancer patients.

This work is in close collaboration with Dr. Andrew Rhim and Dr. Ben Stanger at University of Pennsylvania Medical Center. Their work (to be featured in the Jan 20 2012 issue of Cell) shows that, in mice, pancreas cells can be found in the blood even before the mice develop what we would call cancer. This result is important because it indicates that the spread of pancreatic cancer may start very early in the development of the disease.

The funded work will allow us to show that our GEDI microfluidic device can capture the cells that lead to spread of pancreatic cancer in humans, and allow us to study those cells in detail.