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In ductal adenocarcinoma of the pancreas (PDA), an extensive stromal reaction drives tumour progression and contributes to the lethality of the disease. An understanding of the causes of this desmoplastic response, and the consequent effects of an altered extracellular niche on tumour cell growth, invasion and resistance, would therefore be a pivotal step in the quest to improve patient outcomes.
The inflammatory and fibrotic responses in PDA are the result of complex interplay between tumour and host cells. A universal feature is the generation of a dense and highly rigid stromal extracellular matrix (ECM) that, based on analyses of the adhesion-dependent control of cell phenotype in other systems, is likely to alter proliferation, migration and differentiation. Despite the importance of stromal rigidity to fate determination, a lack of methodologies to manipulate and investigate force sensing in vivo has retarded progress. These methods are now available, so it is timely to determine how stromal rigidity drives tumour progression. The focus of this programme will be the effects of rigidity on proliferation, but our findings will also provide insights into other processes, including metastasis and survival.
The inflammatory and fibrotic responses in PDA are the result of complex interplay between tumour and host cells. A universal feature is the generation of a dense and highly rigid stromal extracellular matrix (ECM) that, based on analyses of the adhesion-dependent control of cell phenotype in other systems, is likely to alter proliferation, migration and differentiation. Despite the importance of stromal rigidity to fate determination, a lack of methodologies to manipulate and investigate force sensing in vivo has retarded progress. These methods are now available, so it is timely to determine how stromal rigidity drives tumour progression. The focus of this programme will be the effects of rigidity on proliferation, but our findings will also provide insights into other processes, including metastasis and survival.
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Journal of Biological Chemistryno. 3 (2024)
Marija Lončarić,Nikolina Stojanović,Anja Rac-Justament,Kaatje Coopmans,Dragomira Majhen, Jonathan D. Humphries,Martin J. Humphries,Andreja Ambriović-Ristov
Cellular & molecular biology lettersno. 1 (2023): 56-23
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (2023)
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Journal of cell scienceno. 19 (2023)
Life science allianceno. 8 (2023): e202201685-e202201685
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biorxiv(2023)
bioRxiv : the preprint server for biology (2023)
JOURNAL OF CELL SCIENCEno. 19 (2023)
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