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Cancer Cell death Cell cycle Cytoskeleton Exo/endocytosis Differentiation Division Organelles Signalling Stem cells Trafficking
Cell Biology International (1996) 20, 481–487 (Printed in Great Britain)
CONSTITUTIVELY MIGRATING MALIGNANT RAT LIVER EPITHELIAL CELLS PRODUCE A MIGRATION-STIMULATING ACTIVITY FOR EPITHELIAL CELLS (eMSA)
BARBARA K. ECKSTEIN and ERNESTO G. BADEf1
Fakultät für Biologie, Universität Konstanz, Postfach 5560 <M 599>, D-78434, Konstanz, Germany


Abstract

Constitutively migrating malignant rat liver epithelial cells obtained by Ha ras transformation exhibit a fibroblastoid phenotypein vitro. The cells deposit the anti-adhesive extracellular matrix (ECM) protein tenascin into their ECM migration tracks. The serum-free medium conditioned by these constitutively migrating cells contains an epithelial migration-stimulating activity (eMSA) that is neither cell-type-, nor species-specific. This eMSA fractionates in the range of 30 to 50kDa and binds to Mono-Q, Mono-S, and with low affinity to heparin–Sepharose. The conditioned medium also induces the expression of the serine proteinase inhibitor PAI-1. Both migration and expression of PAI-1 are inhibited by cyclic AMP, as previously shown for the migration of the non-transformed liver epithelial cells induced by several growth factors that act through tyrosine kinase receptors. These results suggest that the eMSA might act through signal transduction pathways similar to those of the growth factors previously studied. It is postulated that the eMSA, through both autocrine and paracrine mechanisms, is at least partially responsible for the malignant phenotype of the transformants.


Key words: cell migration, invasion, malignant phenotype, autocrine regulation, tenascin, growth factor, liver carcinoma cells, extracellular matrix.

f1To whom correspondence should be addressed.


doi:10.1006/cbir.1996.0063


ISSN Print: 1065-6995
ISSN Electronic: 1095-8355
Published by Portland Press Limited on behalf of the International Federation for Cell Biology (IFCB)