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Researchers Find A Way To Identify Pancreatic Cell Metastasis

Pancreatic cancer is considered to be one of the fatal and most difficult cancers to treat as the variant has a 5-year survival rate of just 5%. This is primarily due to a lack of proper prognosis of the disease, which leads to a more vicious metastasis period infecting other parts of the body.

However, a new report has surfaced which claims that the researchers of Osaka University have come with a method of understanding the molecular mechanisms of pancreatic tumor cells to build effective target treatments.

According to the study published in eLife, the researchers have analyzed that in human pancreatic cancer tissues, there is a signaling protein called the ARL4C that is related to the migratory and invasive properties of the cancer cells. So, the researchers believe that, by tracing the overexpression of this particular protein, metastasis can be identified and treated. ARL4C is a protein that is present in the human body during the fetal development period but in adult tissues, the protein is not found.

The researchers developed cells in the lab and used ARL4C protein to show how it accelerates the spread of cancer in the body of mice. Traditionally, treatments try to target another protein called the KRAS which can lead to certain side effects. But the researchers have noticed that since the ARL4C protein does not have any requirements in the adult body, targeting this protein can limit the metastasis of pancreatic cancer and thereby improve the chances of survival from this disease.

The lead author of the study, Akikazu Harada, said, "We discovered that ARL4C localized to so-called invasive pseudopods - functionally analogous to, but structurally distinct from invadopodia - at the cell surfaces."

Talking about the process of how pancreatic cancer spreads, the paper says that the cancer cells use a certain cell structure called invadopodia, which are feet-like extrusions that exist in cells while invasive pseudopods are larger in diameter than invadopodia. These pseudopods usually reside in the front end of the cell structure.

"In these pseudopods, ARL4C recruited another protein called IQGAP1 - that is also highly expressed in numerous cancers including pancreatic cancer - which transported an enzyme called MMP14 to the pseudopods allowing the cancer cell to break into and invade the collagen gel or extracellular matrix," said the study.

The researchers are using this knowledge to use an antisense oligonucleotide or ASO to block protein production. "An ASO targeted against ARL4C was able to suppress the lymph node metastases of pancreatic cancer cells implanted into the pancreas of an immunodeficient mouse," says Akira Kikuchi, senior author of the study. If ARL4C is blocked, the cancer cells are less aggressive and less likely to spread. Although only preliminary, these findings open up promising novel therapeutic avenues for this extremely aggressive cancer and shed light on its mechanism of metastasis," according to the paper.

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