A diagnosis of pancreatic cancer is pretty damning. With it’s scarily low survival rates, it’s quite safe to say that having pancreatic cancer is pretty much a death sentence. As horrible a truth as it is, it is still the truth – and an embarrassing one at that. Our progress in researching the disease is however beginning to shed light on what was once an empty void of treatment, one that swallowed each and every life it came across. 

A New Fascin-ation

For years now, we have tried to develop screening methods and effective treatments in order to stop the disease in it’s tracks. The problem however has been with the aggression pancreatic cancer shows at spreading around the body, with most people being diagnosed too late for their treatments to make a difference.

We know that pancreatic cancer can spread quickly, something many scientists attribute to the incredible mobility of pancreatic cancer cells. However a specific feature separating pancreatic cancerous cells from normal cells (in terms of mobility) has not been identified or measured before – until now.

A new culprit has joined the line-up, that of a protein called fascin. In normal cells, fascin acts as a cross-linking protein that bundles actin filaments together tightly. Think of it if you will as the gel holding together strands of hair. These filament bundles continuously construct and deconstruct at the membrane of each cell, reaching out into the external environment in the form of “filopodia” to play important roles in cell-cell communication, microenvironment surveillance and motility.

Filopodia not only allow the cell to physically move through its environment but it also allows for critical communications between proteins at the membrane surface. This can result in invasive properties shown by the cell.
Filopodia not only allow the cell to physically move through its environment but it also allows for critical communications between proteins at the membrane surface. This can result in invasive properties shown by the cell.

Tracking Down The Culprit

The idea that fascin is in some way involved in cancer mobility is not new as the protein has been a suspect in cancer motility since its discovery. It is only now through research conducted by Cancer Research UK that evidence is emerging for the involvement of the protein.

The study looked into the effect that a deficiency of fascin would present in murine models as well as measuring fascin in 122 pancreatic cancer samples from humans. Results in mice indicated that a lack of fascin correlated with the development of late-stage pancreatic intraepithelial neoplasia (abnormal cells within a layer of lining cells – pre-invasive) and pancreatic ductal adenocarcinoma (tumours that present in gland ducts – aggressive and metastatic).

A) Normal pancreatic tissue B) pancreatic ductal adenocarcinoma tissue. Fascin is represented in green in both images.
A) Normal pancreatic tissue B) pancreatic ductal adenocarcinoma tissue. Fascin is represented in green in both images.

In human samples, a total of 95% exhibited fascin levels that coincided with decreased overall survival, a high tumour grade and vascular invasion. In mice models, 100% of aggressive samples exhibited detectable fascin levels, coinciding with the protein’s potential as a oncogenic factor. In contrast, only 6% of pre-invasive samples revealed detectable fascin.

From these numbers, it’s pretty clear that the more fascin there is, the more aggressive potential a cancer cell will have. The video below shows footage of the results, explaining in depth the role that fascin plays.

Where To Go From Here?

For once in quite a long time, something has been identified in pancreatic cancer that could be the reason behind its aggressive growth. Identifying fascin as a quantitative effector of tumour cell mobility means it can now be seen as a potential therapeutic target. There are however some issues.

Fascin is a naturally occurring protein within a range of cells, detectable in the nervous system, retinal tissue and the testes. It just so happens that fascin in dramatically upregulated in tumour cells, a finding that is evident also in breast, colon and prostate cancer. The question is, how can fascin be specifically targeted in tumour cells when it is also present in healthy cells? Perhaps then scientists can focus on the driving genetic sequences that are upregulated in cancer cells? The method in which these findings are utilised will be the next challenge for scientists and, if successful, the targeting of fascin has the potential to prevent metastases of usually very mobile cancer types.

With recent research predicting pancreatic cancer to be the second most lethal cancer in the United States by 2030 – overtaking both breast (women)/prostate (men) and colorectal cancer – any form of progress toward identifying a potential target should be considered a success. It is what will be developed from this study that will determine whether pancreatic cancer will remain a “death sentence” for years to come.

Read more:

Li A, et al. (2014) “Fascin Is Regulated by Slug, Promotes Progression of Pancreatic Cancer in Mice, and Is Associated With Patient Outcomes“, Gastroenterology, 146:(5) p.1386-1396.

The “Pancreatic cancer second most deadly by 2030” report.

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