Open Access Symposium

Imaging Cancer: from molecule to man

Date:
23 November 2015 13:30 hrs. - 18:00 hrs.
Location:
Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289
Title:
Imaging Cancer: from molecule to man
Speaker(s):

Diane Lidke, Philippe Chavrier, Anoek Zomer and Erik Aarntzen

Host(s):

Alessandra Cambi, Annemiek van Spriel, Geert van de Bogaart, Mangala Srinivas and Jolanda de Vries, Dept. of Tumor Immunology, RIMLS

23-11-2015 13:30:0023-11-2015 18:00:00Europe/AmsterdamImaging Cancer: from molecule to man Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289Rimlsrimls@radboudumc.nl

Remarks / more information:

Program

13:30-14:10        Diane Lidke (Department of Pathology, University of New Mexico, Albuquerque, USA)

undefinedundefined“Enhanced dimerization drives ligand-independent activity of mutant EGFR in lung cancer”. The epidermal growth factor receptor (EGFR) is a member of the ErbB family of membrane receptor tyrosine kinases that drive cell growth and survival, with roles in normal development and disease pathogenesis.  It is generally accepted that ligand binding to these transmembrane proteins leads to conformational changes, receptor homo- and hetero-oligomerization, kinase activation, and the transphosphorylation of multiple cytoplasmic tail tyrosines.  A wealth of structural data supports a model of EGFR signal initiation through the formation of back-to-back homodimers. However, ligand-occupancy status, dimer lifetimes and structure of the receptor remain to be defined on living cells. Imaging technologies and biological tools have developed to a point where many fundamental biological questions can now be addressed at the molecular level.  In particular, single particle tracking, super-resolution and FRET-FLIM provide information on protein dynamics, distribution and conformation within the plasma membrane.  Using these techniques, we have compared the behavior of wild type and oncogenic mutants of EGFR, revealing new insights into the roles of receptor dynamics and structure in the regulation of receptor interactions that drive tumorigenesis. 

14:10-14:50        Philippe Chavrier (Cell Biology Dept., Institute Curie, Paris, France)

undefined“Mechanism of Matrix Metalloproteinase secretion during breast tumor cell invasion”. The hallmark of a metastatic tumor cells is its ability to disseminate from the primary tumor by degrading the extracellular matrix and basement membranes that form a barrier around the tissue. Remodeling of the extracellular matrix requires formation of actin-based protrusions of the plasma membrane called invadopodia, where the trans-membrane matrix metalloproteinase MT1-MMP accumulates. The nature of carriers that mediate plasma membrane delivery of MT1- MMP, mechanisms underlying MT1-MMP exocytosis and influences of matrix composition and biophysical properties remain poorly understood. I will present evidence that MT1-MMP is required for the transition of in situ carcinoma to invasive breast cancer lesions based on immunohistochemistry analysis and the intraductal xenograft model. At the mechanistic level, I will present data supporting a general exocytic mechanism of MT1-MMP used by tumor cells to breach the basement membrane and for invasive migration through fibrous type collagen-enriched interstitial tissues surrounding the primary tumor. 

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

15:10-15:50        Anoek Zomer (Hubrecht Institute, Cancer Biophysics, Utrecht, The Netherlands)

undefinedundefined“In Vivo Imaging Reveals Extracellular Vesicle-Mediated Phenocopying of Metastatic Behavior”. Tumor progression is driven by the accumulation of mutations and the dynamic behavior of individual cells. Commonly-used techniques such as histology and Western-blot provide a static view of these dynamic processes and/or analyze large numbers of cells, thereby obscuring the adaptive properties of individual cells. By contrast, high-resolution intravital imaging (IVM) through chronically implanted optical windows allows the real-time visualization of dynamic processes for prolonged times in living mice. By combining these IVM techniques with Cre-mediated lineage tracing in fluorescent mouse models, we showed that tumors are highly plastic and very heterogeneous and that the behavior of small sub-population of cells within a tumor is responsible for the growth and spread of cancer. 

15:50-16:30        Erik Aarntzen (Department of Radiology and Nuclear Medicine, Radboudumc, Nijmegen)

undefined“Immune cells in cancer; a new role for in vivo imaging”. Our lab has been among the first to exploit dendritic cell (DC) based vaccinations to treat melanoma patients. Over the past years, we have exploited in vivo imaging to optimize our vaccination strategy and monitor immune responses in vivo. I will highlight how clinical imaging with 111In-oxinate (for scintigraphy) or SPIO (for magnetic resonance), and metabolic tracers such as  [18F]-labeled 3’-fluoro-3’-deoxy-thymidine ([18F]FLT) and a [18F]-labeled fluoro-2’-deoxy-2’-D-glucose ([18F]FDG) for imaging with positron emission tomography (PET) helped us to answer crucial questions. 

16:30-18:00        “Meet the speakers” drinks & snacks (Foyer, 8th floor RIMLS building)



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