The Interaction between Laminin-332 and α3β1 Integrin Determines Differentiation and Maintenance of CAFs, and Supports Invasion of Pancreatic Duct Adenocarcinoma Cells
| Autor: | Johannes A. Eble, Augusto Martins Lima, Martin Stehling, Jörg Haier, Cord Brakebusch, Ana C. Martins Cavaco, Sameer A. Dhayat, Michele F. Caliandro, Maryam Rezaei |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Stromal cell Cell Integrin pancreatic cancer spheroid culture lcsh:RC254-282 Article Metastasis 03 medical and health sciences 0302 clinical medicine Laminin Pancreatic cancer medicine cancer-associated fibroblasts (CAF) biology differentiation medicine.disease invasion lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis biology.protein Cancer research Adenocarcinoma integrin α3β1 Transforming growth factor laminin-332 |
| Zdroj: | Cancers, Vol 11, Iss 1, p 14 (2018) Cancers Volume 11 Issue 1 Cavaco, A C M, Rezaei, M, Caliandro, M F, Lima, A M, Stehling, M, Dhayat, S A, Haier, J, Brakebusch, C & Eble, J A 2019, ' The Interaction between Laminin-332 and α3β1 Integrin Determines Differentiation and Maintenance of CAFs, and Supports Invasion of Pancreatic Duct Adenocarcinoma Cells ', Cancers, vol. 11, no. 1, 14, pp. 1-20 . https://doi.org/10.3390/cancers11010014 |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers11010014 |
| Popis: | Ranking among the most lethal tumour entities, pancreatic duct adenocarcinoma cells invade neighbouring tissue resulting in high incidence of metastasis. They are supported by tumour stroma fibroblasts which have undergone differentiation into cancer-associated fibroblasts (CAFs). Stiffness of cell substratum, cytokines, such as transforming growth factor-β (TGF-β), and stromal matrix proteins, such as laminin-332, are factors which promote CAF differentiation. In a spheroid culture system, differentiation of CAFs was analysed for laminin-332 production, laminin-binding integrin repertoire, adhesion and migration behaviour, and, in heterospheroids, for their interplay with the pancreatic duct adenocarcinoma AsPC-I cells. Our data reveal that CAFs produce laminin-332 thus contributing to its ectopic deposition within the tumour stroma. Moreover, CAF differentiation correlates with an increased expression of α3β1 integrin, the principal laminin-332-receptor. Beyond its role as novel CAF marker protein, integrin α3β1 crucially determines differentiation and maintenance of the CAF phenotype, as knock-out of the integrin α3 subunit reversed the CAF differentiated state. AsPC-I cells co-cultured in heterospheroids with integrin α3-deficient CAFs invaded less than from heterospheroids with wild-type CAFs. This study highlights the role of integrin α3β1 integrin-laminin-332 interaction of CAFs which promotes and sustains differentiation of CAFs and promotes carcinoma invasion. |
| Databáze: | OpenAIRE |
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