Workshop 4: Tumor Heterogeneity and the Microenvironment

(February 2,2015 - February 6,2015 )

Organizers


Alexander Anderson
Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center & Research Institute
Trevor Graham
Tumour Biology, Barts Cancer Institute, QMUL
Michael Ostrowski
Department of Molecular and Cellular Biochemistry, The Ohio State University
Charlie Swanton
London Research Institute

Heterogeneity in cancer is an observed fact, both genetically and phenotypically. Cell-cell variation is seen in almost all aspects of cancer from early development through to invasion and subsequent metastasis. Our current understanding of this heterogeneity has mainly focused at the genetic scale with little information on how this variation translates to actual changes in cell phenotypic behavior. Given that many genotypes can lead to the same cellular phenotype, we must also understand the range and scope of this heterogeneity at the phenotypic scale as ultimately this variability will dictate the aggressiveness of the tumor and its treatability. Central to our understanding of this heterogeneity is how the tumor cells interact with each other and with their microenvironment.

The tumor microenvironment is not simply the extra cellular matrix, but a complex milieu consisting of growth promoting and inhibiting factors, nutrients (including oxygen and glucose), chemokines, and importantly other cell types including (but not limited to) fibroblasts, immune cells, endothelial cells and normal epithelial cells. These microenvironmental factors and different cell types interact with one another and the tumor as it grows. The role of endothelial cells and the immune system in cancer development are fairly well established, but less is known about the function of host fibroblasts in this process. Most solid tumors present as dense fibrotic masses, which suggests that fibroblasts contribute to tumor growth by infiltrating and depositing extracellular matrix proteins. In addition, the phenotype of fibroblasts found within and around tumors (activated fibroblasts or cancer associated fibroblasts: CAFs) is different to normal fibroblasts, and closely resembles myofibroblasts. Fibroblasts act in wound healing, angiogenesis and tissue remodeling by releasing growth factors and proteases such as matrix metalloproteinases. They also deposit matrix proteins such as laminin, tenascin and fibronectin. Therefore, if the growing tumor can co-opt such fibroblasts it has an unlimited source of many of the fundamental elements required for growth and invasion.

The two central themes of this workshop are:

  • Heterogeneity (be it phenotypic, signaling or genotypic), and
  • Microenvironment (ECM, nutrients, fibroblasts and immune cells).

Since a highly heterogeneous tumor has the potential to adapt to any microenvironment, understanding how interactions between the growing tumor and its microenvironment modulate tumor heterogeneity is critical to unraveling the mechanisms of cancer initiation.

Accepted Speakers

Alexander Anderson
Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center & Research Institute
Fran Balkwill
Centre for Cancer and Inflammation, Queen Mary University of London
Mary Helen Barcellos-Hoff
Robert Clarke
Joseph Costello
Christina Curtis
Medicine and Genetics, Stanford University
Robert Gatenby
H. Lee Moffitt Cancer Center & Research Institute
Philip Gerlee
Integrated Mathematical Oncology, Moffitt Cancer Center
Trevor Graham
Tumour Biology, Barts Cancer Institute, QMUL
Simon Hayward
Medical Center, Vanderbilt University
Sui Huang
Cell and Molecular Biology, Northwestern University Medical School
Simon Leedham
Wellcome Trust Centre for Human Genetics, University of Oxford
Gustavo Leone
Molecular Virology, Immunology, and Medical Genetics, The Ohio State University
Morag Park
Biochemistry and Oncology, McGill University
Vito Quaranta
Department of Cancer Biology, Vanderbilt University
Sergio Quezada
Erik Sahai
Tumor Cell Biology Lab, London Research Institute
Richard Sole
Andrea Sottoriva
Centre for Evolution and Cancer, The Institute of Cancer Research
Charlie Swanton
London Research Institute
Zoltan Szallasi
Thea Tlsty
Valerie Weaver
Richard White
Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center
Daniel Worthley
Medicine, University of Adelaide
Yinyin Yuan
Centre for Evolution and Cancer, The Institute of Cancer Research
Monday, February 2, 2015
Time Session
Tuesday, February 3, 2015
Time Session
Wednesday, February 4, 2015
Time Session
Thursday, February 5, 2015
Time Session
Friday, February 6, 2015
Time Session
Name Email Affiliation
Anderson, Alexander alexander.Anderson@moffitt.org Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center & Research Institute
Balkwill, Fran f.balkwill@qmul.ac.uk Centre for Cancer and Inflammation, Queen Mary University of London
Barcellos-Hoff, Mary Helen MHBarcellos-Hoff@nyumc.org
Clarke, Robert clarker@georgetown.edu
Costello, Joseph jcostello@cc.ucsf.edu
Curtis, Christina ccurtis@usc.edu Medicine and Genetics, Stanford University
Gatenby, Robert robert.gatenby@moffitt.org H. Lee Moffitt Cancer Center & Research Institute
Gerlee, Philip philipgerlee@gmail.com Integrated Mathematical Oncology, Moffitt Cancer Center
Graham, Trevor t.graham@qmul.ac.uk Tumour Biology, Barts Cancer Institute, QMUL
Hayward, Simon simon.hayward@vanderbilt.edu Medical Center, Vanderbilt University
Huang, Sui sui.huang@systemsbiology.org Cell and Molecular Biology, Northwestern University Medical School
Leedham, Simon simon.leedham@cancer.org.uk Wellcome Trust Centre for Human Genetics, University of Oxford
Leone, Gustavo gustavo.leone@osumc.edu Molecular Virology, Immunology, and Medical Genetics, The Ohio State University
Lowengrub, John lowengrb@math.uci.edu Mathematics, University of California, Irvine
Ostrowski, Michael michael.ostrowski@osumc.edu Department of Molecular and Cellular Biochemistry, The Ohio State University
Park, Morag morag.park@mcgill.ca Biochemistry and Oncology, McGill University
Quaranta, Vito vito.quaranta@vanderbilt.edu Department of Cancer Biology, Vanderbilt University
Quezada, Sergio s.quezada@ucl.ac.uk
Sahai, Erik erik.sahai@cancer.org.uk Tumor Cell Biology Lab, London Research Institute
Sole, Richard ricard.sole@upf.edu
Sottoriva, Andrea andrea.sottoriva@icr.ac.uk Centre for Evolution and Cancer, The Institute of Cancer Research
Swanton, Charlie charles.swanton@cancer.org.uk London Research Institute
Szallasi, Zoltan zszallasi@chip.org
Tlsty, Thea thea.tlsty@ucsf.edu
Weaver, Valerie valerie.weaver@ucsfmedctr.org
White, Richard whiter@mskcc.org Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center
Worthley, Daniel daniel.worthley@adelaide.edu.au Medicine, University of Adelaide
Yuan, Yinyin yinyin.yuan@icr.ac.uk Centre for Evolution and Cancer, The Institute of Cancer Research