Hollande laboratory: Tumour Heterogeneity in Metastatic Cancer

Researcher

Research Overview

Associate Professor Fred Hollande's research group aims to understand mechanisms that underlie the genetic and non-genetic heterogeneity within individual tumours, and to characterise signalling pathways that specify the differential behaviour of cell subpopulations that drive metastatic progression and treatment response. We are interested to determine the respective contributions of intrinsic programs and of extrinsic/micro-environmental cues in the control of these signalling events.

The group also aims to characterise the molecular mechanisms that underlie the phenotypic plasticity of cancer cells and to understand how this plasticity affects the response of tumour-initiating cells to anti-cancer treatments.

Our interest is in solid tumours with a primary focus on colorectal cancer, a major public health issue and one of the main causes of cancer-related death in Australia and worldwide.

Translational objectives of our work include the discovery of novel biomarkers providing early prognosis and prediction of treatment response, and the improvement of therapeutic efficacy by targeting cells that drive disease relapse after therapy. This is achieved by combining the phenotypic and genotypic analysis of samples freshly obtained from cancer patients and by characterising molecular networks that drive drug resistance in subpopulations of cancer cells.

Benefiting from the collaborative efforts of surgeons, medical oncologists, genomics specialists, statisticians and systems biologists from several VCCC member organisations, this project uses an innovative approach to characterise and target these drug-resistant cancer cell subpopulations.

To do so, Associate Professor Hollande's lab has developed ex vivo models that allow the unbiased analysis of differential responses to drug treatment by individual subpopulations of cancer cells within individual tumours. This will allow the identification of pathways that drive the intrinsic drug-resistance ability of specific cancer cell subpopulations and/or the plasticity behaviours that allow them to adapt and survive during treatment exposure. Preclinical orthotopic graft models are then used to validate the sensitivity of these newly identified targets to pharmacological inhibition.

A broad array of experimental models is used in the team, including 2D and 3D tissue culture, ex vivo analysis of human metastatic tumour samples, live and static cell imaging, flow cytometry, cytotoxicity assays, methylation analysis, genome-wide RNA analysis, and various xenograft models.

Staff

Associate Professor Frederic Hollande – Group Leader, acting Deputy Head of Department
Dr Jai Smith – Post-doctoral Research Fellow
Dr Yuan Cao – Post-doctoral Research Fellow
Dr Momeneh Foroutan – Post-doctoral Research Fellow
Dr Corina Behrenbruch – (MBBS), PhD Student
Ms Carolyn Shembrey – PhD student
Ms Simone Alexander – Master’s Student

Collaborators

National

Professor Mathias Ernst, Dr Michael Buchert – Olivia Newton-John Cancer Research Institute, Melbourne
Professor Alexander Heriot, Dr. Ben Thomson, A/Prof Michael Michael, Prof Robert Ramse – Peter McCallum Cancer Centre, Melbourne
Professor Sean Grimmond, Associate Professor Oliver Hofmann – University of Melbourne Centre for Cancer Research, Melbourne
Dr Melissa Davis – Walter and Elisa Hall Institute, Melbourne
Dr Davide Ferrari – School of Mathematics and Statistics, The University of Melbourne
Professor Andrew Hill – Department of Biochemistry and Genetics, La Trobe University, Melbourne
Dr Ann-Marie Patch – Queensland Institute of Medical Research, Brisbane
Dr Jon Mangum – Department of Pharmacology and Therapeutics, University of Melbourne
Dr Delphine Merino – Olivia Newton John Cancer Research Institute, Melbourne
Dr Erica Sloan – Monash Institute of Pharmaceutical Sciences, Monash University
Dr Tracy Putoczki – Walter and Elisa Hall Institute, Melbourne

International

Prof Alain Puisieux – Cancer Research Center of Lyon, France
Dr Julie Pannequin, Dr Jean Marc Pascussi – Institute of Functional Genomics, Montpellier, France
Associate Professor Sergei Rodin – Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden

Funding

Our group has received funding from the following sources:

  • National Health and Medical research council of Australia (NH&MRC) Project Grant “Volatile Anaesthesia and Cancer Recurrence” (2018-2020)
  • Colorectal Surgical Society of Australia and New Zealand (CSSANZ) Foundation “Genomic analysis of Metastatic Colorectal Cancer” (2018)
  • National Health and Medical Research Institute (INSERM), France, and The University of Melbourne partnership program (2018-2021).
  • Colorectal Surgical Society of Australia and New Zealand (CSSANZ) “Personalising Treatment in Patient with Metastatic Colorectal Cancer” (2016)
  • NH&MRC Project grant "Establishing and validating a new therapeutic target for colon and stomach cancer" (2014-2016)
  • NH&MRC Project grant "Novel Therapeutics for Colon Cancer treatment" (2014-2016)
  • NH&MRC Project grant: "Role of claudin-2 on the development of colorectal cancer metastases and their resistance to treatment" (2013-2016)
  • The University of Melbourne Department of Pathology (2012-2015)

Research Publications

See a complete list of Fred Hollande's publications.

  • Paquet-Fifield S. et al., Tight junction protein claudin-2 promotes self-renewal of human colorectal cancer stem-like cells. Cancer Res. 2018 Jun 1;78(11):2925-2938. doi: 10.1158/0008-5472.CAN-17-1869.
  • Hollande F. Micro-managers of disease: the long and short of miRNA regulation in colorectal cancer. Non-Coding RNA Investigation, Non-coding RNA Investig. 2018;2:23. doi: 10.21037/ncri.2018.04.03
  • Behrenbruch C, et al. Surgical stress response and promotion of metastasis in colorectal cancer: a complex and heterogeneous process. Clin Exp Metastasis. 2018 Apr;35(4):333-345. doi: 10.1007/s10585-018-9873-2.
  • Huynh J, et al. The JAK/STAT3 axis: A comprehensive drug target for solid malignancies. Semin Cancer Biol. 2017 Aug;45:13-22.
  • Morel A-P, et al. A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and breast cancer genome stability. Nature Medicine, 2017 May;23(5):568-578.
  • Mølck C, et al., The A2b adenosine receptor antagonist PSB-603 promotes oxidative phosphorylation and ROS production in colorectal cancer cells via adenosine receptor-independent mechanism Cancer Letters., 2016 Dec 1;383(1):135-143.
  • Qin Y, et al. Laminins and cancer stem cells, partners in crime? Semin Cancer Biol. 2017 Aug;45:3-12. doi: 10.1016/j.semcancer.2016.07.004.
  • Grillet F. et al., Circulating tumor cells from patients with colorectal cancer have cancer stem cell hallmarks in ex-vivo culture. Gut, 2016 Jul 25. pii: gutjnl-2016-311447. doi: 10.1136/gutjnl-2016-311447.
  • Planque C. et al., Pregnane 1 X-receptor promotes stem cell-mediated colon cancer relapse. Oncotarget, 2016 Jul 18. doi: 10.18632/oncotarget.10646.
  • Xie J et al., High expression of TROP2 characterizes different cell subpopulations in androgen-sensitive and androgen-independent prostate cancer cells. Oncotarget. 2016 Jul 12;7(28):44492-44504. doi: 10.18632/oncotarget.9876.
  • Giraud J. et al., Autocrine secretion of progastrin promotes the survival and self-renewal of colon cancer stem-like cells. Cancer Research, 2016 Jun 15;76(12):3618-28.
  • Qian G. et al., Semi-supervised Clustering by Iterative Partition and Regression with Neuroscience Applications. Comput Intell Neurosci. 2016;2016:4037380. doi: 10.1155/2016/4037380.
  • Aeson Chang, Corina Kim-Fuchs, Caroline P Le, Frederic Hollande, Erica K Sloan. Neural Regulation of Pancreatic Cancer: A Novel Target for Intervention. Cancers 2015; Jul 17;7(3): 1292-312. doi: 10.3390/cancers7030838.

Research Projects



Faculty Research Themes

Cancer

School Research Themes

Cancer in Medicine



Key Contact

For further information about this research, please contact Head of Laboratory Associate Professor Fred Hollande

Department / Centre

Clinical Pathology

Unit / Centre

Hollande laboratory: Tumour Heterogeneity in Metastatic Cancer


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