Cancer Stem Cell Conference

av Linda Pudelko, 19 - 24 september 2016

Cancer Stem Cell Conference – Cleveland, 2016

The „Cancer Stem Cell Conference“ organized by the Case Western Reserve University and the National Center for Regenerative Medicine took place in Cleveland, Ohio, September 20-23, 2016. It was the second cancer stem cells meeting (first held in 2014) gathering pioneers and leading scientists in the field of cancer stem cells with numerous talks and interesting poster sessions.

The program started off with a pre-conference workshop focusing on carrier development with talks clarifying grant application and paper publishing processes. As a PhD student, who is just starting to publish papers, it was a great opportunity to listen to the presentations of Christine Weber, editor of Nature Cell Biology, and Deborah Sweet, editor of Cancer Stem Cell, who highlighted the most important steps from manuscript submission to paper acceptance.

In a podium debate around the topic „Cancer Stem Cells: Fact or Fiction“, key note speakers such as Prof. John Dick, Prof. Mina Bissell and Prof. Luis Parada discussed the controversial existence of cancer stem cells. The speakers agreed on the existence of a cancer cell type that displays self-renewal capacity, a fundamental property for long-term tumor propagation. Moreover, the speakers highlighted the important role of the tumor microenvironment to dictate the cancer cell fate towards a more mesenchymal and hence, more stem-cell like state. However, due to the high cell state plasticity, cancer stem cells remain a moving target that does not necessarily require a cellular hierarchy, and up to today, there is no unique marker to identify cancer stem cells.

Regarding the main conference agenda, I highly enjoyed the inspiring presentations of keynote speakers Prof. John Dick, Prof. Mina Bissell and Prof. Luis Parada, as well as talks presenting novel insights and techniques.

Prof. John E. Dick (University of Toronto) was the first to identify cancer stem cells in certain types of human leukemia, thereby presenting a milestone in the cancer stem cell field. In his talk, John Dick presented parts of this pioneering work and provided new insights regarding the origins of relapse. Whole genome sequencing data has revealed that relapse originates from rare LSCs that evolve before diagnosis and survive therapy, meaning that the resistance is already determined before any kind of therapy.

Prof. Mina Bissell (Lawrence Berkeley National Laboratory) has greatly contributed to the field of breast cancer research by studying the role of the extracellular matrix (ECM) and the nucleus environment to gene expression in normal and malignant tissue. In her talk, Mina Bissell highlighted the important role of the tumor microenvironment regarding cellular decision-making and maintenance of homeostasis in addition to already known defense mechanisms such as DNA repair. She postulated that the (malignant) transformation of cells is context-dependent and that the phenotype is more dominant than the genotype, again suggesting that the architecture (or TME) is crucial for the cell fate.

Prof. Luis Parada (Memorial Sloan Kettering) is a developmental biologist who uses genetically engineered mouse models to study brain tumors, cancer stem cells and tumor progression. In his presentation, he focused on the cells of origin and cancer stem cells in malignant glioma. It is well known that chemotherapy targets rapidly dividing cells, but not stem cells, even though they acquire new mutations during therapy. Moreover, his group has shown that highly aggressive glioblastomas arise from stem cells but not from more differentiated cells when knocking out classical driver genes in mouse tumor models. These cells are insensitive to Temozolomide therapy and mostly reside in the subventricular zone (SVZ).  His group was able to detect inherent cancer stem cell heterogeneity as some cancer stem cells display  GFP high (+++) signals for a more quiescent state and GFP low (+) signals when transitionally amplifying. The characterization of GFP+++ cells have revealed that they are able to give rise to the largest neurospheres and to enter the cell cycle upon asymmetrical division, meaning to give rise to both GFP+++ and GFP+. Moreover, GFP+++ populations can give rise to the entire tumor hierarchy in 4 generations (Ki67) and possess high transplantation and infiltration capacity. Contradicting the results of other groups, the de-differentiation of cancer stem cells has not been observed (which might be assay-specific).

In addition to the keynote presentations, I greatly benefitted from several short talks. Amongst others, Sonia E. Voiculescu (Einstein College of Medicine) presented an innovative method for high resolution imaging of lungs to investigate the real time development of the metastatic microenvironment and properties of cancer stem cell behavior in vivo. Julie Pannequin (Institut de Génomique Fonctionelle, France) presented a technique to isolate and culture circulating tumor cells (CTCs) of colorectal cancer followed by functional assays. CTCs were directly isolated from blood samples of colorectal cancer patients and used for therapeutic screening and decision-making. Moreover, Julie highlighted the importance of optimal culture conditions such as the right medium as well as hypoxic conditions. Chris Hubert (Cleveland Clinic) presented a novel method to model glioblastoma in vitro by using cancer stem cell organoids. Glioblastoma organoids display several advantages compared to monolayer cultures: they are able to grow for several weeks and recapitulate the human tumor heterogeneity really well. Chris was able to detect GSCs heterogeneity in his glioblastoma organoids (e.g. Olig2/Sox2++: at outer rim, but Sox2+ in the middle,) as well as more dividing cells (Ki67+). Additionally, when transplanted into mice, organoids give rise to more infiltrative tumors in vivo compared to monolayer cultures. Regarding downstream applications, this model is also suitable for high-throughput screens, hence improving glioblastoma drug development.

I would like to end my travel report by thanking Radiumhemmets forskningsfonder for granting me the financial support to participate at the Cancer Stem Cell Conference. In addition to the informative talks, presenting my own research in one of the poster sessions enriched me with productive feedback and offered a beneficial platform to interact with other participants. Overall, it was a great opportunity to network with leading scientists and cancer stem cell experts from all over the world, and I return to the lab with new insights, ideas and inspirations.