BEGIN:VCALENDAR
PRODID:-//Columba Systems Ltd//NONSGML CPNG/SpringViewer/ICal Output/3.3-
 M3//EN
VERSION:2.0
CALSCALE:GREGORIAN
METHOD:PUBLISH
BEGIN:VEVENT
DTSTAMP:20171030T110108Z
DTSTART:20171103T130000Z
DTEND:20171103T140000Z
SUMMARY:In situ mechanobiology of epithelia in health and disease
UID:{http://www.columbasystems.com/customers/uom/gpp/eventid/}r19p-j9e2q7
 yz-sgulxh
DESCRIPTION:The onset of metastasis occurs when cancer cells invade and b
 reach the basement membrane (BM) that provides mechanical support to epi
 thelial tissues. Yet\, it remains unclear what triggers cancer cells to 
 breach the BM\, and how ‘triggered’ cells breach the BM. We have establi
 shed an in vitro assay using the native BM interface for culturing epith
 elial cells and have demonstrated that native BMs isolated from human ti
 ssues act as a native substrate for culturing epithelial cells in terms 
 of composition\, architecture and stiffness. These are required to act j
 ointly in order to achieve apico-basal polarity\, tissue barrier formati
 on and stiffness properties of the epithelial layer similarly to secreto
 ry epithelia in vivo. During cancer progression in vivo\, cancer cells c
 an perforate BM using proteolysis and the cancer cell invasion is associ
 ated with decreased cellular stiffness and correlated to changes in cell
  and BM morphology. The role of stromal cells in this process has not ye
 t been resolved. Therefore\, we examined if carcinoma-associated fibrobl
 asts (CAFs) isolated from cancer patients promoted cancer cell invasion 
 through a BM. In the presence of CAFs\, moderately invasive cancer cells
  invade in a matrix metalloproteinase-independent manner. Using live ima
 ging and atomic force microscopy\, we showed that CAFs actively pull\, s
 tretch and soften the BM\, forming gaps through which cancer cells can m
 igrate. By exerting contractile forces\, CAFs alter the organization and
  physical properties of native BM\, making it permissive for cancer cell
  invasion. Finally\, we propose that\, in addition to proteolysis\, mech
 anical interactions between CAFs and BM represent an alternative mechani
 sm of BM breaching. Given their mechano-biological relevance\, native BM
 s allow us to further understand mechano-signaling processes between epi
 thelia and surrounding stromal layers at the BM interface in physiologic
 al and pathological states.
STATUS:TENTATIVE
TRANSP:TRANSPARENT
CLASS:PUBLIC
LOCATION:Lecture Theatre\, Michael Smith Building\, Manchester
END:VEVENT
END:VCALENDAR