2nd Open Access Symposium

Imaging cancer: from molecule to man

Date:
21 November 2016 13:30 hrs. - 17:30 hrs.
Location:
Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289
Title:
Imaging cancer: from molecule to man
Host(s):

Alessandra Cambi, Annemiek v. Spriel, Geert v.d. Bogaart, Mangala Srinivas & Jolanda de Vries, RIMLS

21-11-2016 13:30:0021-11-2016 17:30:00Europe/AmsterdamImaging cancer: from molecule to man Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289Rimlsrimls@radboudumc.nl

Remarks / more information:


Flyer

Organized within the MIN02 course “Visualizing health and disease: from molecule to man” and the MIN04 course “Cancer mechanisms and personalized medicine”

Program

13:30-14:10        Mangala Srinivas (Dept. of Tumor immunology, Radboud UMC, Nijmegen)

Imaging and the optimization of dendritic cell therapy in melanoma
undefinedDendritic cells (DCs) are key regulators of the immune system. DC therapy has proved to be a viable form of therapy for melanoma, to the extent that this is now covered by health insurance in the Netherlands. However, the therapy is far from optimal; we still need to optimise the number of cells, the site of injection and many other parameters. In vivo imaging is essential for us to answer such questions, and potentially also to tailor the therapy for individual patients. In this talk, I will discuss the role of whole body imaging, such as MRI, PET and SPECT in the optimization of DC therapy in melanoma patients. 

14:10-14:50        Danijela Vignjevic (Institute Curie, Paris, France)

Fibroblasts induce protease-independent cancer cell invasion
undefinedAt the stage of carcinoma in situ, the basement membrane (BM) segregates tumor cells from the stroma. This barrier must be breached to allow dissemination of the tumor cells to adjacent tissues. Cancer cells can perforate the BM using proteolysis. Whether stromal cells also play a role in this process is unknown. Here we show that carcinoma-associated fibroblasts (CAFs) isolated from colon cancer patients promote cancer cell invasion through a mesenteric BM. In the presence of CAFs, cancer cells invade in a matrix metalloproteinase-independent manner. Using live imaging and atomic force microscopy, we found that CAFs actively pull, stretch and soften the BM, forming gaps through which cancer cells can migrate. By exerting contractile forces, CAFs alter the organization and the physical properties of the BM, making it permissive for cancer cell invasion. We propose that, in addition to proteolysis, mechanical forces exerted by CAFs represent an alternative mechanism of BM breaching. 

14:50-15:10         Coffee break (Foyer) 

15:10-15:50        Jacky Goetz (INSERM, Strasbourg, France)

Tracking rare and dynamic events in vivo at high resolution using multimodal correlative microscopy
undefinedThree reasons explain why most of the critical events driving normal and pathological scenarios had been less investigated: they occur rarely in space and time, they are highly dynamic, they differ when studied in situ in an entire living organism. Metastasis is the primary cause for cancer-related mortality, but its mechanisms remain to be elucidated. Intravital imaging has opened the door to in vivo functional imaging in animal models of cancer, however it is limited in resolution. Ultrastructural analysis of tumor metastasis in vivo has so far been hindered by the limited field of view of the electron microscope, making it difficult to retrieve volumes of interest in complex tissues. We recently developed a multimodal correlative approach allowing us to rapidly and accurately combine functional in vivo imaging with high-resolution ultrastructural analysis of tumor cells in a relevant pathological context. The multimodal correlative approach that we propose here combines two-photon excitation microscopy (2PEM), microscopic X-ray computed tomography (microCT) and three-dimensional electron microscopy (3DEM). It enables a rapid and accurate correlation of functional imaging to high-resolution ultrastructural analysis of tumor cells in a relevant pathological context. As an example, we are now capable of providing high- and isotropic (8nm) resolution imaging of single metastasizing tumor cells previously imaged in the process of extravasation in the living mouse brain. This reliable and versatile workflow offers access to ultrastructural details of metastatic cells with an unprecedented throughput opening to crucial and unparalleled insights into the mechanisms of tumor invasion, extravasation and metastasis in vivo. 

15:50-16:30        Annemiek van Spriel (Dept. of Tumor immunology, Radboudumc, Nijmegen)

Tetraspanin CD37 protects against the development of B cell lymphoma.
undefinedWorldwide, B cell non-Hodgkin lymphoma is the most common hematological malignancy which represents a substantial clinical problem. The molecular events that lead to B cell lymphoma are only partially defined. We discovered that deficiency of tetraspanin CD37, which is important for B cell function, induces the development of B cell lymphoma. The underlying mechanism was constitutive signaling through the IL-6 pathway. Loss of CD37 on neoplastic cells in patients with diffuse large B-cell lymphoma is directly correlated with worse progression-free and overall survival. Together, this study identifies CD37 as a novel tumor suppressor that directly protects against B cell lymphomagenesis. 

16:30-17:30        “Meet the speakers” drinks & snacks (Foyer, 8th floor RIMLS building)



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