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Invasion of Reconstituted Basement Membrane Matrix by Metastatic Human Tumor Cells¹

Department of Anatomy and Division of Oral Biology, Schools of Dentistry and Medicine, University of California, San Francisco, California 94143 [R. H. K., J. W.], and Department of Pathology, School of Medicine, Stanford University, Stanford, California 94305 [K. G. B.]

A gel-like reconstituted basement membrane matrix containing type IV collagen, laminin, entactin, nidogen, and heparan sulfate proteoglycan was used to examine the invasive properties of human HT1080 fibrosarcoma cells. Within several hours after seeding, the tumor cells initiated a random migration, leaving behind channels etched in the surface of the matrix. Eventually the channels became interconnected into a complex network. As the tumor cells proliferated, the channels became filled until the surrounding matrix was gradually dissolved. Cells then migrated outward, forming the typical disorganized cell monolayer normally observed when fibrosarcoma cells are cultured on plastic surfaces. In contrast to the fibrosarcoma cells, normal skin fibroblasts, while able to attach to the matrix, exhibited minimal migration, tracking, and invasion during the same time period. When tumor cells were seeded onto thick layers of matrix, the cells ultimately invaded downward into the matrix, leaving behind open tunnels. At the front of the invading cells, long irregular pseudopodia projected in the direction of movement. Electron microscopy demonstrated these filopodial and lamellopodial projections to directly extend into the surrounding matrix, with focal clearing of the matrix in the immediate vicinity of these invading pseudopodia. Thus, tumor cell invasion of extracellular matrices, including basal lamina, may proceed by the formation of specialized pseudopodia that not only form adhesion contacts with the matrix but also provide an efficient mechanism for the focal hydrolysis of the matrix at the site of directed cell movement.

¹ Supported by NIH Grant CA 33834.

² To whom requests for reprints should be addressed, at HSW-604, Department of Anatomy, University of California, San Francisco, CA 94143.

Received 7/16/85. Revised 12/ 2/85. Accepted 1/ 2/86.

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