Article 4N5B5 Key To Targeting The Spread Of Pancreatic Cancer

Key To Targeting The Spread Of Pancreatic Cancer

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Arthur T Knackerbracket has found the following story:

An international team of researchers has revealed how aggressive pancreatic cancer cells change their environment to enable easy passage to other parts of the body (or metastasis) -- the main cause of pancreatic cancer related death.

The researchers discovered that some pancreatic tumours produce more of a molecule called 'perlecan' to remodel the environment around them, which helps cancer cells spread more easily to other parts of the body, and also protects them against chemotherapy. In a mouse model, the researchers showed that lowering the levels of perlecan revealed a reduction in the spread of pancreatic cancer and improved response to chemotherapy.

[...] The Garvan-led team investigated why some pancreatic cancers spread, while others appear to stay in one place. In their study, the researchers took an unconventional path -- they compared the tissue around tumour cells in both metastatic (spreading) and non-metastatic (non-spreading) pancreatic cancers. This tissue -- known as the 'matrix' -- acts like a glue that holds different cells in an organ or in a tumour together.

Using mouse models, the team extracted fibroblasts -- cells that produce most of the matrix -- from spreading and non-spreading pancreatic tumours. By mixing these different fibroblasts with cancer cells, the researchers found that remarkably, cancer cells from a non-spreading tumour began to spread when mixed with fibroblasts from a spreading tumour.

"Our results suggest that some pancreatic cancer cells can 'educate' the fibroblasts in and around the tumour. This lets the fibroblasts remodel the matrix and interact with other, less aggressive cancer cells in a way that supports the cancer cells' ability to spread," says first author Dr Claire Vennin.

CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan, Nature (DOI: 10.1038/s41467-019-10968-6)

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