Tumor Microenvironment Laboratory 

Seano Giorgio-Uriel Chantraine Institut Curie

Giorgio Seano Team Leader Tel:

Brain tumors are composed of primary tumors of the central nervous system – such as glioblastoma (GBM) – and secondary metastatic tumors – such as melanoma and lymphoma as well as lung and breast cancers. Brain tumors are highly lethal and unfortunately not many improvements have been achieved to improve the survival of these patients.

Microenvironment of the brain perivascular niche (from Seano, Curr; Opin Oncol. 2018)
Fig. 1: Microenvironment of the brain perivascular niche (from Seano, Curr; Opin Oncol. 2018)

Resistance mechanisms in brain tumors
Brain tumors are intrinsically resistant to therapy – radio or chemotherapy – and the recurrence rate is very high. Chemoradiation resistance is one of the most clinically-relevant challenges faced in patients with brain tumors. A key patho-physiological hub where resistance to therapy is developed is the perivascular niche (Fig. 1). Brain tumors are among the most densely vascularized tumors (Fig. 2). This increases the possibility for the tumor cells to take advantage from the frequent brain perivascular niches. The understanding of the cellular crosstalk established within the brain tumor perivascular niche might provide us with key discoveries of new brain tumors vulnerabilities.

Live imaging of perfused vasculature in a mouse brain with glioblastoma (5th at the 2015 Nikon small world Competition)
Fig. 2: Live imaging of perfused vasculature in a mouse brain with glioblastoma (5th at the 2015 Nikon small world Competition)

Preclinical models and intravital microscopy
Our overall strategy is to use state-of-the-art intravital imaging technologies (Fig. 3) that allow us to dynamically visualize subclasses of tumor cells in their in vivo microenvironment with single-cell resolution. We also extensively use patient material to reconstitute a “patient-in-a-dish” model, by following a “bench-to-bedside and bedside-to-bench” strategy.

Funding and collaborations
Our team is currently supported by the ATIP-Avenir program (CNRS and INSERM), a collaborative intramural grant (PIC3), a co-funded European PhD position (IC-3i PhD program) and selected by ARC JCJC (declined grant).

Multi-photon imaging of the brain cortex vasculature, blood flow (top) and endothelial cells (bottom)
Fig. 3: Multi-photon imaging of the brain cortex vasculature, blood flow (top) and endothelial cells (bottom)

We have assembled a network of numerous, highly experienced and supportive collaborators, which will provide my research group with the multidisciplinary expertise necessary to accomplish this innovative and ambitious project, such as Drs. Marie Dutreix (Institut Curie, radiation biology), Pierre Verrelle and Philip Poortmans (Institut Curie, radiation oncology), Chiara Villa (Hôpital Foch, neuropathology), Claire Lugassy (Institut Curie, experimental oncology), Raymond Barnhill (Institut Curie, anatomic pathology), Hiroaki Wakimoto (Dana-Farber/Harvard Cancer Center, neurosurgery), Sylvie Roberge (Harvard Medical School, animal surgery) and Darine Abi Haidar (Orsay Campus, optics and microscopy).

Dr. Seano authored 26 articles, presented 16 seminars on his research, reviewed 15 papers and received 2 prestigious prizes, 2 travel grants and 5 competitive grants/fellowships for his studies. His scientific interests are tumor angiogenesis, vessel co-option, cell migration and resistance mechanisms. In 2017, he was selected as a Junior Group Leader in Institut Curie Research Center and he is now setting up his new laboratory.

 

Key publications

Year of publication 2018

Amelie Griveau, Giorgio Seano, Samuel J Shelton, Robert Kupp, Arman Jahangiri, Kirsten Obernier, Shanmugarajan Krishnan, Olle R Lindberg, Tracy J Yuen, An-Chi Tien, Jennifer K Sabo, Nancy Wang, Ivy Chen, Jonas Kloepper, Louis Larrouquere, Mitrajit Ghosh, Itay Tirosh, Emmanuelle Huillard, Arturo Alvarez-Buylla, Michael C Oldham, Anders I Persson, William A Weiss, Tracy T Batchelor, Anat Stemmer-Rachamimov, Mario L Suvà, Joanna J Phillips, Manish K Aghi, Shwetal Mehta, Rakesh K Jain, David H Rowitch (2018 Apr 24)

A Glial Signature and Wnt7 Signaling Regulate Glioma-Vascular Interactions and Tumor Microenvironment.

Cancer cell : DOI : S1535-6108(18)30125-9
Ethel R Pereira, Dmitriy Kedrin, Giorgio Seano, Olivia Gautier, Eelco F J Meijer, Dennis Jones, Shan-Min Chin, Shuji Kitahara, Echoe M Bouta, Jonathan Chang, Elizabeth Beech, Han-Sin Jeong, Michael C Carroll, Alphonse G Taghian, Timothy P Padera (2018 Mar 24)

Lymph node metastases can invade local blood vessels, exit the node, and colonize distant organs in mice.

Science (New York, N.Y.) : 1403-1407 : DOI : 10.1126/science.aal3622
Giorgio Seano (2017 Nov 15)

Targeting the perivascular niche in brain tumors.

Current opinion in oncology : 54-60 : DOI : 10.1097/CCO.0000000000000417

Year of publication 2016

Teresa E Peterson, Nathaniel D Kirkpatrick, Yuhui Huang, Christian T Farrar, Koen A Marijt, Jonas Kloepper, Meenal Datta, Zohreh Amoozgar, Giorgio Seano, Keehoon Jung, Walid S Kamoun, Trupti Vardam, Matija Snuderl, Jermaine Goveia, Sampurna Chatterjee, Ana Batista, Alona Muzikansky, Ching Ching Leow, Lei Xu, Tracy T Batchelor, Dan G Duda, Dai Fukumura, Rakesh K Jain (2016 Apr 5)

Dual inhibition of Ang-2 and VEGF receptors normalizes tumor vasculature and prolongs survival in glioblastoma by altering macrophages.

Proceedings of the National Academy of Sciences of the United States of America : 4470-5 : DOI : 10.1073/pnas.1525349113

Year of publication 2014

Giorgio Seano, Giulia Chiaverina, Paolo Armando Gagliardi, Laura di Blasio, Alberto Puliafito, Claire Bouvard, Roberto Sessa, Guido Tarone, Lydia Sorokin, Dominique Helley, Rakesh K Jain, Guido Serini, Federico Bussolino, Luca Primo (2014 Sep 15)

Endothelial podosome rosettes regulate vascular branching in tumour angiogenesis.

Nature cell biology : 931-41, 1-8 : DOI : 10.1038/ncb3036

Year of publication 2013

Giorgio Seano, Giulia Chiaverina, Paolo Armando Gagliardi, Laura di Blasio, Roberto Sessa, Federico Bussolino, Luca Primo (2013 Mar 9)

Modeling human tumor angiogenesis in a three-dimensional culture system.

Blood : e129-37 : DOI : 10.1182/blood-2012-08-452292
All publications