{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:38:49Z","timestamp":1791416329340,"version":"4.3.3"},"reference-count":57,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,1,20]]},"abstract":"<jats:p>Invasive tumor dissemination in vitro and in vivo involves the proteolytic degradation of ECM barriers. This process, however, is only incompletely attenuated by protease inhibitor\u2013based treatment, suggesting the existence of migratory compensation strategies. In three-dimensional collagen matrices, spindle-shaped proteolytically potent HT-1080 fibrosarcoma and MDA-MB-231 carcinoma cells exhibited a constitutive mesenchymal-type movement including the coclustering of \u03b21 integrins and MT1\u2013matrix metalloproteinase (MMP) at fiber bindings sites and the generation of tube-like proteolytic degradation tracks. Near-total inhibition of MMPs, serine proteases, cathepsins, and other proteases, however, induced a conversion toward spherical morphology at near undiminished migration rates. Sustained protease-independent migration resulted from a flexible amoeba-like shape change, i.e., propulsive squeezing through preexisting matrix gaps and formation of constriction rings in the absence of matrix degradation, concomitant loss of clustered \u03b21 integrins and MT1-MMP from fiber binding sites, and a diffuse cortical distribution of the actin cytoskeleton. Acquisition of protease-independent amoeboid dissemination was confirmed for HT-1080 cells injected into the mouse dermis monitored by intravital multiphoton microscopy. In conclusion, the transition from proteolytic mesenchymal toward nonproteolytic amoeboid movement highlights a supramolecular plasticity mechanism in cell migration and further represents a putative escape mechanism in tumor cell dissemination after abrogation of pericellular proteolysis.<\/jats:p>","DOI":"10.1083\/jcb.200209006","type":"journal-article","created":{"date-parts":[[2003,1,21]],"date-time":"2003-01-21T15:48:39Z","timestamp":1043164119000},"page":"267-277","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":1252,"title":["Compensation mechanism in tumor cell migration"],"prefix":"10.1083","volume":"160","author":[{"given":"Katarina","family":"Wolf","sequence":"first","affiliation":[{"name":"1Department of Dermatology, University of Wu\u0308rzburg, 97080 Wu\u0308rzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Mazo","sequence":"additional","affiliation":[{"name":"2Department of Pediatrics, Children's Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Leung","sequence":"additional","affiliation":[{"name":"3Department of Pathology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Engelke","sequence":"additional","affiliation":[{"name":"3Department of Pathology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich H.","family":"von Andrian","sequence":"additional","affiliation":[{"name":"4Center for Blood Research, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena I.","family":"Deryugina","sequence":"additional","affiliation":[{"name":"5The Burnham Institute, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex Y.","family":"Strongin","sequence":"additional","affiliation":[{"name":"5The Burnham Institute, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva-B.","family":"Bro\u0308cker","sequence":"additional","affiliation":[{"name":"1Department of Dermatology, University of Wu\u0308rzburg, 97080 Wu\u0308rzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Friedl","sequence":"additional","affiliation":[{"name":"1Department of Dermatology, University of Wu\u0308rzburg, 97080 Wu\u0308rzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2003,1,13]]},"reference":[{"key":"2023072214021460900_BIB1","doi-asserted-by":"crossref","first-page":"5872","DOI":"10.1074\/jbc.270.11.5872","volume":"270","year":"1995","journal-title":"J. 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