Cancer-Recurrence SIGNED
Tumor cell death supports recurrence of cancer
Total Cost €
0EC-Contrib. €
0Partnership
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Project "Cancer-Recurrence" data sheet
The following table provides information about the project.
| Coordinator |
STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS
Organization address contact info |
| Coordinator Country | Netherlands [NL] |
| Project website | https://www.nki.nl/divisions/molecular-pathology/van-rheenen-j-group/ |
| Total cost | 2˙000˙000 € |
| EC max contribution | 2˙000˙000 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2014-CoG |
| Funding Scheme | ERC-COG |
| Starting year | 2015 |
| Duration (year-month-day) | from 2015-09-01 to 2020-08-31 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS | NL (AMSTERDAM) | coordinator | 1˙564˙393.00 |
| 2 | KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW | NL (AMSTERDAM) | participant | 435˙606.00 |
Map
Project objective
Introduction: Current anti-cancer treatments are often inefficient, while many patients initially benefit from anti-cancer drugs eventually experience relapse of resistant tumors throughout the body. Current clinical strategies mainly aim at inducing tumor cell death, but this induction may have unintentional and unwanted side effects on surviving tumor cells.
Preliminary data: We show that after chemotherapy-induced initial regression, PyMT mammary tumors reappear. During regression, we observe an increased number of cells that have undergone epithelial-mesenchymal transition (EMT) and become migratory. We show that migration can be induced upon uptake of extracellular vesicles (e.g. apoptotic bodies). Our findings suggest that EMT is induced upon chemotherapy, through e.g. EV uptake, potentially leading to migration and growth of surviving cells.
Hypothesis and main aim: Based on preliminary data, we hypothesize that tumor cell death induces migration and growth of the surviving tumor cells. We aim to identify the key cell types and mechanisms that mediate this effect, and establish whether interference with these cells and mechanisms can reduce recurrence of tumors after chemotherapy.
Approach: We have developed unique intravital imaging tools and genetically engineered fluorescent mice to visualize and characterize if and how dying tumor cells can affect surrounding surviving tumor and stromal cells. We will test whether dying tumor cells can influence the growth, migration, dissemination and metastasis of surviving tumor cells directly or indirectly through stromal cells. We will identify potential targets to block the influence of the dying tumor cells, and test whether this blockade inhibits the unintended side-effects of tumor cell death.
Conclusion: With the studies proposed in this grant, we will gain fundamental insights on how induction of tumor cell death, the universal aim of therapy, could play a role in growth and spread of surviving tumor cells.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2016 |
Evelyne Beerling, Ilse Oosterom, Emile Voest, Martijn Lolkema, Jacco van Rheenen Intravital characterization of tumor cell migration in pancreatic cancer published pages: e1261773, ISSN: 2165-9087, DOI: 10.1080/21659087.2016.1261773 |
IntraVital 5/3 | 2019-07-25 |
| 2018 |
Arianna Fumagalli, Saskia J E Suijkerbuijk, Harry Begthel, Evelyne Beerling, Koen C Oost, Hugo J Snippert, Jacco van Rheenen, Jarno Drost A surgical orthotopic organoid transplantation approach in mice to visualize and study colorectal cancer progression published pages: 235-247, ISSN: 1754-2189, DOI: 10.1038/nprot.2017.137 |
Nature Protocols 13/2 | 2019-07-25 |
| 2017 |
Lotte Bruens, Saskia I.J. Ellenbroek, Jacco van Rheenen, Hugo J. Snippert In Vivo Imaging Reveals Existence of Crypt Fission and Fusion in Adult Mouse Intestine published pages: 674-677.e3, ISSN: 0016-5085, DOI: 10.1053/j.gastro.2017.05.019 |
Gastroenterology 153/3 | 2019-07-25 |
| 2017 |
Saskia J.E. Suijkerbuijk, Jacco van Rheenen From good to bad: Intravital imaging of the hijack of physiological processes by cancer cells published pages: 328-337, ISSN: 0012-1606, DOI: 10.1016/j.ydbio.2017.04.015 |
Developmental Biology 428/2 | 2019-07-25 |
| 2017 |
Maria Alieva, Andreia S. Margarido, Tamara Wieles, Erik R. Abels, Burcin Colak, Carla Boquetale, Herke Jan Noordmans, Tom J. Snijders, Marike L. Broekman, Jacco van Rheenen Preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-017-07660-4 |
Scientific Reports 7/1 | 2019-07-25 |
| 2018 |
Koen C. Oost, Lisa van Voorthuijsen, Arianna Fumagalli, Rik G.H. Lindeboom, Joep Sprangers, Manja Omerzu, Maria J. Rodriguez-Colman, Maria C. Heinz, Ingrid Verlaan-Klink, Madelon M. Maurice, Boudewijn M.T. Burgering, Jacco van Rheenen, Michiel Vermeulen, Hugo J.G. Snippert Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene published pages: 1600-1614, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2018.01.033 |
Cell Reports 22/6 | 2019-07-25 |
| 2017 |
Arianna Fumagalli, Jarno Drost, Saskia J. E. Suijkerbuijk, Ruben van Boxtel, Joep de Ligt, G. Johan Offerhaus, Harry Begthel, Evelyne Beerling, Ee Hong Tan, Owen J. Sansom, Edwin Cuppen, Hans Clevers, Jacco van Rheenen Genetic dissection of colorectal cancer progression by orthotopic transplantation of engineered cancer organoids published pages: E2357-E2364, ISSN: 0027-8424, DOI: 10.1073/pnas.1701219114 |
Proceedings of the National Academy of Sciences 114/12 | 2019-07-25 |
| 2016 |
Evelyne Beerling, Daniëlle Seinstra, Elzo de Wit, Lennart Kester, Daphne van der Velden, Carrie Maynard, Ronny Schäfer, Paul van Diest, Emile Voest, Alexander van Oudenaarden, Nienke Vrisekoop, Jacco van Rheenen Plasticity between Epithelial and Mesenchymal States Unlinks EMT from Metastasis-Enhancing Stem Cell Capacity published pages: 2281-2288, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2016.02.034 |
Cell Reports 14/10 | 2019-07-25 |
| 2017 |
Edouard Hannezo, Colinda L.G.J. Scheele, Mohammad Moad, Nicholas Drogo, Rakesh Heer, Rosemary V. Sampogna, Jacco van Rheenen, Benjamin D. Simons A Unifying Theory of Branching Morphogenesis published pages: 242-255.e27, ISSN: 0092-8674, DOI: 10.1016/j.cell.2017.08.026 |
Cell 171/1 | 2019-07-25 |
| 2017 |
Scheele, Colinda L. G. J.; Hannezo, Edouard; Muraro, Mauro J.; Zomer, Anoek; Langedijk, Nathalia S. M.; van Oudenaarden, Alexander; Simons, Benjamin D.; van Rheenen, Jacco Identity and dynamics of mammary stem cells during branching morphogenesis published pages: , ISSN: 1476-4687, DOI: 10.17863/CAM.8101 |
Nature 1 | 2019-07-25 |
| 2016 |
C. Prunier, V. Josserand, J. Vollaire, E. Beerling, C. Petropoulos, O. Destaing, C. Montemagno, A. Hurbin, R. Prudent, L. de Koning, R. Kapur, P. A. Cohen, C. Albiges-Rizo, J.-L. Coll, J. van Rheenen, M. Billaud, L. Lafanechere LIM Kinase Inhibitor Pyr1 Reduces the Growth and Metastatic Load of Breast Cancers published pages: 3541-3552, ISSN: 0008-5472, DOI: 10.1158/0008-5472.can-15-1864 |
Cancer Research 76/12 | 2019-07-25 |
| 2016 |
Léon van Gurp, Cindy J. M. Loomans, Pim P. van Krieken, Gitanjali Dharmadhikari, Erik Jansen, Femke C. A. S. Ringnalda, Evelyne Beerling, Jacco van Rheenen, Eelco J. P. de Koning Sequential intravital imaging reveals in vivo dynamics of pancreatic tissue transplanted under the kidney capsule in mice published pages: 2387-2392, ISSN: 0012-186X, DOI: 10.1007/s00125-016-4049-6 |
Diabetologia 59/11 | 2019-07-25 |
| 2016 |
Nobuo Sasaki, Norman Sachs, Kay Wiebrands, Saskia I. J. Ellenbroek, Arianna Fumagalli, Anna Lyubimova, Harry Begthel, Maaike van den Born, Johan H. van Es, Wouter R. Karthaus, Vivian S. W. Li, Carmen López-Iglesias, Peter J. Peters, Jacco van Rheenen, Alexander van Oudenaarden, Hans Clevers Reg4 + deep crypt secretory cells function as epithelial niche for Lgr5 + stem cells in colon published pages: E5399-E5407, ISSN: 0027-8424, DOI: 10.1073/pnas.1607327113 |
Proceedings of the National Academy of Sciences 113/37 | 2019-07-25 |
| 2016 |
Sophia Frentzas, Eve Simoneau, Victoria L Bridgeman, Peter B Vermeulen, Shane Foo, Eleftherios Kostaras, Mark R Nathan, Andrew Wotherspoon, Zu-hua Gao, Yu Shi, Gert Van den Eynden, Frances Daley, Clare Peckitt, Xianming Tan, Ayat Salman, Anthoula Lazaris, Patrycja Gazinska, Tracy J Berg, Zak Eltahir, Laila Ritsma, Jacco van Rheenen, Alla Khashper, Gina Brown, Hanna Nyström, Malin Sund, Steven Van Laere, Evelyne Loyer, Luc Dirix, David Cunningham, Peter Metrakos, Andrew R Reynolds Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases published pages: 1294-1302, ISSN: 1078-8956, DOI: 10.1038/nm.4197 |
Nature Medicine 22/11 | 2019-07-25 |
| 2016 |
Colinda L.G.J. Scheele, Carrie Maynard, Jacco van Rheenen Intravital Insights into Heterogeneity, Metastasis, and Therapy Responses published pages: 205-216, ISSN: 2405-8033, DOI: 10.1016/j.trecan.2016.03.001 |
Trends in Cancer 2/4 | 2019-07-25 |
| 2018 |
D. J. Huels, L. Bruens, M. C. Hodder, P. Cammareri, A. D. Campbell, R. A. Ridgway, D. M. Gay, M. Solar-Abboud, W. J. Faller, C. Nixon, L. B. Zeiger, M. E. McLaughlin, E. Morrissey, D. J. Winton, H. J. Snippert, J. van Rheenen, O. J. Sansom Wnt ligands influence tumour initiation by controlling the number of intestinal stem cells published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-03426-2 |
Nature Communications 9/1 | 2019-07-25 |
| 2018 |
Maria Alieva, Jacco van Rheenen, Marike L. D. Broekman Potential impact of invasive surgical procedures on primary tumor growth and metastasis published pages: 319-331, ISSN: 0262-0898, DOI: 10.1007/s10585-018-9896-8 |
Clinical & Experimental Metastasis 35/4 | 2019-07-25 |
| 2018 |
Sander C Steenbeek, Thang V Pham, Joep de Ligt, Anoek Zomer, Jaco C Knol, Sander R Piersma, Tim Schelfhorst, Rick Huisjes, Raymond M Schiffelers, Edwin Cuppen, Connie R Jimenez, Jacco van Rheenen Cancer cells copy migratory behavior and exchange signaling networks via extracellular vesicles published pages: e98357, ISSN: 0261-4189, DOI: 10.15252/embj.201798357 |
The EMBO Journal 37/15 | 2019-07-25 |
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