Since we already reported that heparin inhibits the adhesion and locomotion as well as the invasion and metastasis of tumor cells, here we investigated the physiologic effect of heparin on the cellular communications carried out by a numerical analysis of the networks of colonies grown on plastic dishes, supposing that chemical reactions between colonies affect the growth of colonies. Geometric modeling by Voronoi and Delaunay provided computer simulations for the functional role of network communications such as those of control, heparin and computer-colonies by a program, AGNA (Applied Graphics and Network Analysis). It showed that colonies distributed unevenly in the form of two-dimensional optimal spacing (Voronoi domain), and that hub colonies developed in the networks having a greater number of the degree of node were not randomly distributed, but they resulted from the selective growth (connection) of colony communications (attachment), which allowed them to be heterogeneous distribution in size. The average minimum distance between colonies was shortest in control, while the degree of nodes, coefficient of clusters, and entropy were greater in control than those of heparin and computer-colonies. The increment of entropy in the control colonies was able to promote the augmentation of the functional information (chemical reactions), which is larger enough than those of heparin treated colonies indicating that the growth of control colony is greater than that of heparin. These results suggests that heparin inhibits not only cellular growth and locomotion, but also physiologic network communications between colonies.
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