Molecular Analysis of Motility in Metastatic Mammary Adenocarcinoma Cells.
Annual rept. 26 Aug 96-25 Aug 97,
YESHIVA UNIV NEW YORK
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We report upon our studies 1 evaluating the relative roles of lamellipod extension and ruffling in metastatic behavior and 2 developing high resolution methods for localizing important cytoskeletal proteins to the leading edge of EGF-stimulated cells. 1 Addition of EiF or TFa to metastatic NffLn3 cells results in the rapid extension of flat lamellipods. Nonmetastatic MTC cells do not express EF receptor and show extensive ruffling in even in the absence of stimulation. Upon expression of the human EGF receptor in MTC cells, their metastatic ability is increased. In addition, stimulation of the EGF receptor results in transient suppression of ruffling and extension of lamellipods. We conclude that lamellipod extension, and not ruffling, is best correlated with metastatic ability. 2 In order to better identify proteins directly involved in stimulation of actin polymerization at the leading edge, we are developing methods for EM colocalization of newly polymerized actin with specific proteins with appropriate biochemical properties. Our preliminary results show highly improved resolution of the site of EiF-stimulated actin polymerization.
- Medicine and Medical Research