Opinion piece Intercellular invasion and the organizational stability of tissues : a role for ¢bronectin Peter B. Armstrong *, Margaret T. Armstrong Department of Molecular and Cellular Biology, University of California, One Shields Avenue, Davis, CA 95616-8535, USA Received 1 November 1999; accepted 5 January 2000 Abstract Intracellular invasion is the movement of cells of one type into the fabric of other, contiguous tissues. Invasion is a signature behavior of the malignant tumor and also is found as part of the normal behavior of inflammatory blood cells and tissues engaged in the morphogenetic movements of normal embryogenesis and in a number of instances of normal and pathological tissue remodeling in the adult. Informed by the view that the underlying mechanisms of invasion will be similar for tumor cells and invasive blood and embryonic cells, this review adopts a comparative approach to the analysis of invasion. Invasion results in the development of a diffuse interface between contiguous tissues. Its alternative is the maintenance of stable, planar tissue boundaries. This is the more usual condition for contiguous tissues in the animal. This review will focus on the processes that, on the one hand, stabilize planar contact interfaces between tissues, and, on the other, promote the destabilization of tissue integrity by fostering intercellular invasion. Particular attention is devoted to a role for adhesive interactions mediated by the matrix adhesion molecule, fibronectin. In certain instances, fibronectin in the matrix promotes invasion whereas in others, the presence of fibronectin prevents invasion. The distinction appears to depend on whether the invasive tissue is migrating into an acellular extracellular matrix or whether invasion involves densely cellular tissues. In the first instance, fibronectin promotes invasion, whereas in the second, it stabilizes the interface of the contacting tissues and prevents invasion. ß 2000 Elsevier Science B.V. All rights reserved. Keywords : Fibronectin ; Intercellular invasion ; Heart development ; Cell adhesion 1. Introduction The malignant neoplasm is characterized by pro- gressive growth and the ability to disseminate tumor cells beyond the boundaries of the parent tumor. Invasion is responsible for the dissemination of neo- plastic tissue into contiguous normal tissues and is essential for both the intravasation and extravasation steps of the metastatic cascade [1,2]. In this context, invasion, the intrusion of the cells of one tissue into the fabric of contiguous tissues, is an important con- tributor to the pathology of neoplastic disease. How- ever, invasive cell migration is also a normal feature of the migration of in£ammatory blood cells to sites of infection, of the migration of cells engaged in wound healing and angiogenesis, and in several of the episodes of the directed cell migration seen dur- ing normal embryonic development (for review see [3]). Invasion may involve the migration of coherent columns of the invading tissue into the fabric of the host tissue (Fig. 1A) or may be in¢ltrative, where 0304-419X / 00 / $ ^ see front matter ß 2000 Elsevier Science B.V. All rights reserved. PII:S0304-419X(00)00003-2 * Corresponding author. Fax: +1-530-752-3085; E-mail : pbarmstrong@ucdavis.edu Biochimica et Biophysica Acta 1470 (2000) O9^O20 www.elsevier.com/locate/bba