Stimulation of Haptotaxis and Migration of Tumor Cells by Serum Spreading Factor

A central feature of tumor metastasis is the migration of malignant cells through interstitial tissues and vascular structures as they spread throughout the body. Various components of the extracellular matrix and of basement membranes, consisting of genetically distinct coilagens, proteoglycans, and noncollagenous glycoproteins, are known to modulate certain aspects of cell behavior, including cell movement. Serum spreading factor is a glycoprotein component of human serum that is also found in interstitial tissues. Two native forms are seen in human serum, a M_r 65,000 and a M_r 75,000 component. Spreading factor promotes substratum attachment and spreading of diverse cell types, including epithelial and fibroblastic cells, and will affect the growth rate and differentiation of cells in serum-free culture media. Serum spreading factor was shown to promote the directed migration of the following tumor cell lines in modified Boyden chamber assays: murine melanoma K-1735 (clones M2, M4, and 16); human breast carcinoma MCF-7; and human fibrosarcoma HT-1080. The stimulation of movement occurred over a concentration range of 0.5 to 50 μg of serum spreading factor per ml with a maximum response between 5 and 10 μg/ml. The maximal response varied with the cell line and ranged from 5- to 50-fold greater migration than control. A monoclonal antibody to spreading factor, previously shown to inhibit the attachment and spreading-promoting activity, abrogated this migration response. Experiments using filters that were precoated with spreading factor indicated that cells could migrate on an insoiubilized layer of this protein by haptotaxis. Tumor cell migration to spreading factor in vitro suggests a possible role for this protein in the phenotypic behavior of metastatic cells.