Research units - Invasion and Metastasis

Invasion and Metastasis

The Invasion and Metastasis Unit (St Vincent’s Institute and Department of Surgery, Melbourne University) arose in 1997 through the Victorian Breast Cancer Research Consortium (VBCRC), a consortium of Melbourne Medical Research Institutes and the Cancer Council of Victoria that operates as an 'institute without walls'

Research Overview

Cancer cells can move from the primary tumour and spread in the body to form a new cancer deposit known as a ‘secondary’ tumour or ‘metastasis’. Our studies on breast cancer metastasis focus on molecular and cellular processes that are instrumental in the metastatic process, and have a particular focus on extracellular matrix. We have three major areas: (i) matrix metalloproteinases (MMP), which are enzymes that cells use to cut through tissue, (ii) epithelial mesenchymal plasticity (EMP), a spectrum of changes in the shape, behaviour and motility of cells that assist cells in the metastatic process, and (iii) mammographic density (MD), a familial trait that confers 4 to 6 -fold increased risk of developing breast cancer, and likely involves extracellular matrix. We study MMP and EMP to better understand how breast cancer metastasizes so that better diagnostics and therapies can be developed. Each of these projects is directed towards translational (‘bench-to-bedside’) outcomes and is conducted in an arena of clinical interaction with colleagues at St. Vincent’s Hospital.

Research Themes

Epithelial Mesenchymal Plasticity in Breast Cancer Progression

Interplay between hypoxia, c-myb, oestrogen and Snail2 during epithelial mesenchymal transitions (EM

Matrix Metalloproteinases in Breast Cancer Growth and Progression

Molecular and cellular basis of mammographic density in breast cancer

Honours and PhD Projects

Molecular regulation of breast cancer EMP

Integrin-linked kinase (ILK) in breast cancer therapy

Matrix metalloproteinase (MMP) 13 in breast cancer growth and progression

Molecular and cellular basis of mammographic density in breast cancer

Staff

Staff image

Prof Erik (Rik) Thompson
Dr Bryce van Denderen
Dr Honor Hugo
Dr Manisha Shah
Tony Blick
Devika Gunasinghe
Dr Annet Hammacher
Dexing Huang
Hilda Lau
Cletus Pinto
Eliza Soo
Anthony Tachtsidis
Dr Eva Tomaskovic-Crook
Edwin Widodo

Publication Highlights

  1. Lafleur MA, Drew AF, de Sousa EL, Blick T, Bills MM, Walker EC, Williams ED, Waltham M, Thompson EW. Upregulation of matrix metalloproteinases (MMPs) in breast cancer xenografts: A major induction of stromal MMP-13. Int. J. Cancer 114:544-54 (2005) Cover Illustration
  2. Price JT, Quinn JMW, Sims NA, Moore J, Waldeck K, Docherty SE, Myers D, Nakamura A, Waltham M, Gillespie MT, Thompson EW. The HSP90 inhibitor, 17-AAG, enhances osteoclast formation and potentiates bone metastasis of a human breast cancer cell line. Cancer Res. 65:4929-38 (2005)
  3. Lee JM, Dedhar S, Kalluri R, Thompson EW. The epithelial-mesenchymal transition: New insights in signalling, development and disease. J. Cell Biol. 172:973-81 (2006)
  4. Lafleur MA, Mercuri FA, Ruangpanit N, Seiki M, Sato H, Thompson EW. Type-I collagen abrogates the clathrin-mediated internalization of membrane-type-1 matrix metalloproteinase (MT1-MMP) via the MT1-MMP hemopexin domain. J. Biol. Chem. 281:6826-40 (2006)
  5. Hugo H, Ackland ML, Blick T, Lawrence MG, Clements JA, Williams ED, Thompson EW. Epithelial-mesenchymal and mesenchymal-epithelial transitions in carcinoma progression. J. Cell. Physiol. 213:374-83 (2007)
  6. Blick T, Widodo E, Hugo H, Waltham M, Lenburg ME, Neve RM, Thompson EW. Epithelial mesenchymal transition traits in human breast cancer cell lines. Clin. Exp. Metast. 25:629-42 (2008)
  7. Little CB, Barai A, Burkhardt D, Smith SM, Fosang AJ, Werb Z, Shah M, Thompson EW. Matrix metalloproteinase-13 deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development. Arthritis and Rheumatism 60:3723-33 (2009)
  8. Thompson EW, Warton K, Blick T, Wafai R, Hill P, Stanley K. Multiplexed tandem polymerase chain reaction on a single formalin-fixed paraffin-embedded section for breast cancer diagnosis and research. Pathology 42:165-72 (2010)
  9. Tomaskovic-Crook E, Thompson EW, Thiery JP. Epithelial to mesenchymal transition and breast cancer. Breast Cancer Res. 11(6):213 (2009) (Epub. Nov. 9, 2009) Invited review 
  10. Tilkorn DJ, Lokmic Z, Chaffer CL, Mitchell GM, Morrison WA, Thompson EW. Disparate companions: Tissue engineering meets cancer research. Cells Tissues Organs (In press)