Tumor-stroma interactions in gastrointestinal cancers

Our current projects focus on how TGF-β and BMP ligands influence interaction between epithelial tumour cells, CAFs and infiltrating immune cells in vitro and in vivo and to explore clinical applications of these findings. We make use of advanced in vitro and in vivo  mouse model for colorectal- pancreatic- and liver cancer. Our research has a strong translational character emphasized by collaborations with the LUMC medical research profile area Cancer Pathogenesis and Therapy. Our work is supported by grants from the Dutch Cancer society/ Alpe d’HuZes, Stichting Fonds Oncologie Holland (SFOH), Stichting Sacha Swarttouw-Hijmans and Tracon Pharmaceuticals. A summary for laymen (in Dutch) can be found here.


Biosketch:

After obtaining his Master’s degree in Biopharmaceutical Sciences (2003), Luuk Hawinkels (1980) performed a translational research project at the Gastroenterology department of the LUMC. He focused on the interplay between tumour cells and the tumour stroma, unravelling its role in CRC progression and metastasis. After obtaining his PhD in 2009, he joined the ten Dijke/TGF-β group, to work on the role of the TGF-β (co-)receptors endoglin and ALK1 in tumour angiogenesis. 

In 2011 Luuk was awarded the Alpe d’HuZes Bas Mulder Award (personal grant) to explore the role of endoglin in metastasis formation, and started to establish his own independent research line. His early translational research focused on how the endoglin-dependent interaction between cancer- and stroma cells influences metastatic spread of tumours. In January 2015 his group moved to the Gastroenterology department, who have appointed him as assistant professor and a member of the scientific staff in 2016. 

PhD students ongoing:

Lennart van der Burg

Mark Schoonderwoerd

PhD students Completed:

Dr. Madelon Paauwe (2017) 
https://openaccess.leidenuniv.nl/bitstream/handle/1887/45876/front.pdf?sequence=3 

Internships:

We always have research projects available for bachelor and master students with (bio-)medical and biopharmaceutical background. Please contact us via: L.J.A.C.Hawinkels@LUMC.nl or +31 71 526 6736 

Selected publications:

Paauwe M, Heijkants RC, Oudt CH, van Pelt GW, Cui C,  Theuer CP, Hardwick JC, Sier CF,  Hawinkels LJEndoglin targeting inhibits tumor angiogenesis and metastatic spread in breast cancer Oncogene 2016 Aug 4;35(31):4069-79 https://www.ncbi.nlm.nih.gov/pubmed/26804178 

Hawinkels L*, Garcia de Vinuesa A*, Paauwe M, Kruithof-de Julio M, Soullié T, Wiercinska E, Pardali E, Mezzanotte L, Keereweer S, Braumuller T, Heijkants R, Jonkers J, Löwik C,  Goumans MJ1, ten Hagen T and ten Dijke P Activin Receptor-like Kinase 1 Ligand Trap Reduces Microvascular Density and Improves Chemotherapy efficiency to Various Solid Tumors. Clin Cancer Res. 2016 Jan 1;22(1):96-106.Sep 15. pii: clincanres.0743.2015. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/26373572 

Coffelt SB, Kersten K, Doornebal CW, Weiden J, Vrijland K, Hau CS, Verstegen NJ, Ciampricotti M, Hawinkels LJ, Jonkers J, de Visser KE, IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Nature. 2015 Jun 18;522(7556):345-8 https://www.ncbi.nlm.nih.gov/pubmed/25822788 

Hawinkels LJ, Paauwe M, Verspaget HW, Wiercinska E, van der Zon JM, van der Ploeg K, Koelink PJ, Lindeman JH, Mesker W, ten Dijke P, Sier CF. Interaction with colon cancer cells hyperactivates TGF-β signaling in cancer-associated fibroblasts. Oncogene. 2014 Jan 2;33(1):97-107. https://www.ncbi.nlm.nih.gov/pubmed/23208491

Hawinkels LJ
, Garcia de Vinuesa A, Ten Dijke P
. Activin receptor-like kinase 1 as a target for anti-angiogenesis therapy. Expert Opin Investig Drugs. 2013 Nov;22(11):1371-83.Epub 2013 Sep 21. Review https://www.ncbi.nlm.nih.gov/pubmed/24053899

Paauwe M, ten Dijke P, Hawinkels LJEndoglin for tumor imaging and targeted cancer therapy. Expert Opin Ther Targets. 2013 Apr;17(4):421-35. Epub 2013 Jan 17. Review. https://www.ncbi.nlm.nih.gov/pubmed/23327677

Hawinkels LJ, Ten Dijke P. Exploring anti-TGF-β therapies in cancer and fibrosis. Growth Factors. 2011 Aug;29(4):140-52. Epub 2011 Jun 30. Review. https://www.ncbi.nlm.nih.gov/pubmed/21718111

Hawinkels LJ, Kuiper P, Wiercinska E, Verspaget HW, Liu Z, Pardali E, Sier CF, ten Dijke P Matrix metalloproteinase-14 (MT1-MMP)-mediated endoglin shedding inhibits tumor angiogenesis. Cancer Res. 2010 May 15;70(10):4141-50. Epub 2010 Apr 27. https://www.ncbi.nlm.nih.gov/pubmed/20424116

Cunha SI, Pardali E, Thorikay M, Anderberg C, Hawinkels L, Goumans MJ, Seehra J, Heldin CH, ten Dijke P, Pietras K. Genetic and pharmacological targeting of activin receptor-like kinase 1 impairs tumor growth and angiogenesis. J Exp Med. 2010 Jan 18;207(1):85-100.Epub 2010 Jan 11. https://www.ncbi.nlm.nih.gov/pubmed/20065063

Hawinkels LJ, Zuidwijk K, Verspaget HW, de Jonge-Muller ES, van Duijn W, Ferreira V, Fontijn RD, David G, Hommes DW, Lamers CB, Sier CF  VEGF release by MMP-9 mediated heparan sulphate cleavage induces colorectal cancer angiogenesis. Eur J Cancer. 2008 Sep;44(13):1904-13.Epub 2008 Aug 6. https://www.ncbi.nlm.nih.gov/pubmed/18691882