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Cancer-Recurrence SIGNED

Tumor cell death supports recurrence of cancer

Total Cost €

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EC-Contrib. €

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Partnership

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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
address: PLESMANLAAN 121
city: AMSTERDAM
postcode: 1066 CX
website: www.nki.nl

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 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.

# participants  country  role  EC contrib. [€] 
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
List of publications.
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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