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SUMMARY:Cancer Metastasis: Collective Invasion and Cell. Guidance in Heter
 ogeneous Multicellular Systems - Mr Adrien Hallou\, CUED
DTSTART:20131022T130000Z
DTEND:20131022T140000Z
UID:TALK48513@talks.cam.ac.uk
CONTACT:Ms Helen Gardner
DESCRIPTION:Metastasis\, a complex and multistep process\, accounts for mo
 re than 90% of cancer fatalities. The specific features of malignant cells
  such as uncontrolled growth\, altered metabolism and invasive behaviours 
 constitute the hallmarks of cancer [1]. Recent studies have highlighted th
 e importance of the tumour\nmicroenvironment on these signatures of cancer
  and on the onset of metastasis [2].\nAll these factors have been associat
 ed with numerous biological determinants resulting both from an accumulati
 on of genes mutations and a malfunction of\nnumerous regulatory signaling 
 pathways. Owing to the heterogeneity in these factors across different can
 cers and patients\, no common mechanistic pathway leading to metastasis in
 duction and progression has yet been characterized [1\,2\,3].\nIn contrast
  to these tremendous variations of genotype and phenotype\, most solid tum
 ours display similar collective invasion behaviours [3]. The cohesive mult
 icellular structures formed during invasion such as cell sheets\, strands 
 or clusters display stunning morphological similarities and identical mech
 anical behaviours across most cancer pathologies and patients [3\,4]. This
  homogeneity in\nterms of morphology and migration behaviours suggest that
  the invasion stage of metastasis could be mainly controlled by physical i
 nteractions between cells and\nsimple mechanical phenomena [4].\nUsing a n
 ewly introduced computational framework [5]\, we study the collective dyna
 mics of a cancer cell population enclosed in a mechanically resistive\ntis
 sue. We observe that simple physical rules are sufficient to account for s
 ome of the common morphologies of invading tumours\, including regimes of 
 individual and collective invasions [6]. Moreover\, the introduction of a 
 few fibroblast-like cells\, with\nan enhanced ability to remodel the tumou
 r microenvironment\, leads to a strong increase in the invasiveness of the
  cancer cell population. Their invasion behaviour is here associated with 
 the frequent occurrence of “cell fingers”\, guided by fibroblastlike c
 ells at their leading edge [6].\nOverall our in silico experiments reprodu
 ce the phenomenology of invasion across the different cancer pathologies a
 nd provide new insights on the mechanisms\ncontrolling this complex phenom
 enon [6]. Based on simple biophysical hypotheses and generic cellular inte
 ractions\, we believe that our approach will help to unfold the different 
 biological contributions to metastasis and to disentangle the links betwee
 n\ngenes\, environment and malignancy.
LOCATION:Cambridge University Engineering Department\, Oatley meeting room
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