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DTSTART:20171029T020000
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DTSTAMP:20260424T102303Z
UID:5a840dba63a4e862542821@ist.ac.at
DTSTART:20180221T110000
DTEND:20180221T120000
DESCRIPTION:Speaker: John Condeelis\nhosted by Michael Sixt\nAbstract: Ultr
 a-high resolution multiphoton microscopy of live animals in real time led 
 to the discovery of cause and effect relationships between cells leading t
 o metastasis\, relationships otherwise not possible to identify using in v
 itro models. This has revolutionized our understanding of cancer metastasi
 s. Multiphoton imaging at subcellular resolution in vivo demonstrates that
  tumor cells form migratory streams with macrophages and move with high pe
 rsistence to blood vessels under the control of HGF gradients (1). Once at
  the blood vessel\, a cell complex involving the direct contact between a 
 Mena-Hi tumor cell\, endothelial cell and macrophage forms the Tumor Micro
 Environment of Metastasis (TMEM). The TMEM structure itself\, as well as t
 he gene expression pattern of tumor cells interacting with TMEM\, have bee
 n validated as prognostic markers for predicting metastasis in breast canc
 er patients (2\, 3). These were the first markers of metastasis in clinica
 l use derived from multiphoton intravital imaging.Intravital imaging has d
 efined the mechanisms associated with the function of TMEM: a) Streaming t
 umor cells approaching TMEM in vivo use collagen fibers with diameters les
 s than 3 um where cells move the fastest with highest persistence on the n
 arrowest fibers (700 nm  2.5 m)\; b) These increased migration speeds and 
 persistence are associated with the alignment of actomyosin fibers and foc
 al adhesions along the collagen fibers axial dimension thereby increasing 
 axial force production and suppressing turning frequency\;  c) As the high
  speed stream approaches TMEM it results in tumor cell crowding around TME
 M causing MenaINV expression in cancer cells in response to macrophage-ind
 uced NOTCH signaling (4)\; d)  MenaINV expression supports invadopodium as
 sembly and insertion between endothelial cells leading to transendothelial
  migration at TMEM (5)\; e) TMEM is the only site in breast tumors where t
 umor cell transendothelial migration and intravasation occur (6)\; f) TMEM
  are stable structures found at both primary and metastatic tumor sites in
  breast cancer patients (7). Using the above information we have designed 
 treatment strategies for inhibiting TMEM function and metastasis (8\, 9). 
 These treatment strategies are now in clinical trials in breast cancer pat
 ients at sites in North American (clinical trials study number NCT02824575
 ).
LOCATION:Mondi Seminar Room 2\, Central Building\, ISTA
ORGANIZER:astawick@ist.ac.at
SUMMARY:John Condeelis: Cell migration mechanics during tumor cell dissemin
 ation and metastasis
URL:https://talks-calendar.ista.ac.at/events/1112
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