Fibroblasts present in pancreatic tumours produce large amounts of proteins, which promote the proliferation of cancer cells, as well as their ability to metastasize. We have shown that these fibroblasts can be targeted using a somatostatin analogue SOM230, a molecule already used clinically to treat patients with endocrine tumors.
Using cells isolated from pancreatic tumours, various preclinical models of pancreatic cancer, as well as tumor samples from pancreatic cancer patients, we have demonstrated that SOM230 modifies the pro-tumor inflammatory response within the microenvironment, particularly by blocking the production of a cytokine, CSF-1, by fibroblasts. This inhibition reduces the occurrence of metastases, notably when SOM230 is combined with the chemotherapy gemcitabine. Since gemcitabine reduces itself the primary tumor growth, we reveal a complementary therapeutic action of the both drugs gemcitabine and SOM230, on the primary tumor and on metastases, respectively.
We conclude that the combination of SOM230 and chemotherapy represents a novel promising therapeutic strategy, to reduce the appearance of metastases.
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
Key words :
- Intracellular antibodies,
- targeted degradation,
- antibody-based degraders,
- cell-based screening
Collaborations and thanks
- Hôpitaux de Limoges et Beaujon
- Plateforme protéomique, IPBS, Toulouse
- Novartis
- Fondation pour la Recherche Médicale FRM
- Ligue Nationale Contre le Cancer
- INCa
Contact :
Dr. Rémi Samain & Dr. Corinne Bousquet
Centre de Recherches en Cancérologie – Equipe 6
Mail : corinne.bousquet@inserm.fr
One picture
Immunofluorescence confocal image of CSF-1 (green), sst1 (red) and cytokeratin-19 (CK-19, purple) in a patient-derived pancreatic cancer tissue, showing the co-expression of sst1 and CSF-1 in the stroma (fibroblasts) surrounding cancer cells (purple).
