Normalization of protein secretions in the tumor microenvironment blocks metastasis in pancreatic cancer
Fibroblasts in pancreatic tumours produce large amounts of proteins, which promote the proliferation of cancer cells and their ability to metastasise. We have shown that these fibroblasts can be targeted using a somatostatin analogue SOM230, a molecule already used clinically for the treatment of patients with endocrine tumours.
Using cells isolated from pancreatic tumours, different pre-clinical models of pancreatic cancer, as well as tumour samples from pancreatic cancer patients, we have shown that SOM230 normalises the pro-tumour inflammatory response within the microenvironment, particularly by blocking the production of a cytokine, CSF-1, by fibroblasts. This effect reduces the appearance of metastases, particularly under the condition of chemotherapeutic treatment (gemcitabine) which reduces tumour volume, revealing the complementary effect of the two drugs SOM230 and gemcitabine.
We propose that the combination of SOM230 and gemcitabine chemotherapy represents a particularly promising new therapeutic strategy for reducing the occurrence of metastases.
Collaborations and acknowledgements
- Limoges and Beaujon Hospitals
- Proteomic platform, IPBS, Toulouse
- Foundation for Medical Research FRM
- National League Against Cancer
Discover the published article
Cell Mol Gastroenterol Hepatol. 2021 Jan 19;S2352-345X(21)00014-X.doi: 10.1016/j.jcmgh.2021.01.008. Online ahead of print.
Pharmacological normalization of pancreatic cancer-associated fibroblast secretome impairs pro-metastatic cross-talk with macrophages: Stromal CSF-1 facilitates metastasis
R Samain, A Brunel, T Douché, M Fanjul, S Cassant-Sourdy, J Rochotte, J Cros, C Neuzillet, J Raffenne, C Duluc, A Perraud, J Nigri, V Gigoux, I Bieche, M Ponzo, G Carpentier, I Cascone, R Tomasini, H A Schmid, M Mathonnet, R Nicolle, M P Bousquet, Y Martineau, S Pyronnet, C Jean, C Bousquet
Toulouse Cancer Research Center (Oncopole)
Toulouse – FR
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