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Arrangement of variant phenotypes in ordered spatial assemblies during division of stem cells is essential for the selforganization of cell tissues. The cellular patterns of phenotypes competing for space and resources against one another are mostly driven by secreted diffusible chemical signaling clues. This complex process is carried out within a chronological framework of interplaying intracellular and intercellular events. This includes receiving external stimulants- whether secreted by other individuals or provided by the environment interpreting these environmental signals and incorporating the information to designate cell fate. An enhanced understanding of the building blocks of this framework would be of help to set the scene for promising regenerative therapies. In this study, by proposing a designative computational map, we show that there is a correspondence between signaling and developmental patterns that are produced by competing cells. That is, the model provides an appropriate prediction for the final structure of the differentiated cells in a competitive environment. Besides, given that the final state of the cellular organization is known, the corresponding regressive signaling patterns are partly predictable following the proposed map.

BackgroundAbout 90% of cancer-related deaths are due to metastasis of cancer cells and angiogenesis is a critical step in this process. sFLT01 is a novel fusion protein and a dual targeting agent that neutralizes both VEGF and PlGF proangiogenic activities. GRP78 dual effect in tumor growth and angiogenesis could be activated under VEGF stimulation. The current study was designed to investigate the inhibitory impact of sFLT01 protein on VEGF/GRP78 axis. To this point, sFLT01 construct was synthesized, recombinant plasmid was expressed in eukaryotic host cells, sFLT01-HisTag protein was extracted and analyzed. The functional activity of sFLT01 on VEGF-enhanced tube formation and angiogenesis of HUVEC cells were examined. Eventually, the inhibitory impact of sFLT01 on growth and invasiveness and migration of human prostate cancer cell line, DU145, was assessed. Real-time PCR evaluated the level of GRP78 and its effect on the downstream factors; matrix metallopeptidase proteins 2&9 (MMP2&9) along with tissue inhibitor of metalloproteinase proteins1&2 (TIMP1&2). Results According to the data, sFLT01 protein showed modulatory impact on proliferation, invasion, and migration of DU145 cells along with the potential of HUVECs angiogenesis. Real-Time PCR analysis depicted a significant downregulation in GRP78, MMP2 and MMP9 transcripts’ levels, and a subsequent elevation of TIMP1 and TIMP2 expression under sFLT01 stimulation was detected. Conclusion Overall, these data indicated that the inhibitory impact of sFLT01 on cancer cells growth and invasiveness could be mediated through the modulation of VEGF/GRP78/MMP2&9 axis and activation of TIMPs.

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