The growth of many types of cancer cells can be controlled by surrounding normal cells. However, mechanisms underlying this phenomenon have not been defined. We used a layered culture system to investigate how nontransformed cells suppress the growth of neighboring transformed cells. Direct physical contact between transformed and nontransformed cells was required for growth suppression of transformed cells in this system; communication by diffusible factors was not sufficient. However, significant gap junctional communication was not required, indicating that other intercellular junctions mediated this growth regulatory response. We also report that the Src kinase activity in transformed cells was not directly inhibited by contact with nontransformed cells. Instead, nontransformed cells increased the expression of serum deprivationresponse protein and the transcription factor four and a half LIM domain 1 in tumor cells. In addition, these results suggest mechanisms by which normal cells may block Wnt signaling, inhibit insulin-like growth factor activity, and promote host recognition of neighboring tumor cells.
The response of fibroblasts to the conversion of fibrinogen into fibrin was investigated to clarify the relationship between the conversion and wound healing. The formation of fibrin by thrombin little affected fibroblast attachment and morphology. In contrast cells rapidly attached and subsequently spread on fibrin cross-linked by activated Factor XIII. The introduction of cross-linking also stimulated cell proliferation. However neither enzyme had much effect on cellular behavior. These results indicate that the introduction of cross-linking by activated Factor XIII directly promotes the cellular responses, and suggest that the formation of fibrin stabilized by cross-linking plays a significant role not only in stoppage of blood flow but also in subsequent migration and proliferation of fibroblasts.
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