Normal Wound Healing and Tumor Angiogenesis as a Game of Competitive Inhibition.
Normal Wound Healing and Tumor Angiogenesis as a Game of Competitive Inhibition.
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DOI：
10.1371/journal.pone.0166655
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Klement GL
中科院分区：
文献类型：
--
作者：
Kareva I;Abou-Slaybi A;Dodd O;Dashevsky O;Klement GL
通过顺序、精心安排的生长刺激剂和抑制剂的释放，可以减轻正常的伤口愈合和肿瘤血管生成。这些调节剂以时间和空间受控的方式从活化内皮部位形成的血小板凝块中释放，其释放顺序取决于它们对细胞外基质内的糖胺聚糖（GAG）如硫酸乙酰肝素（HS）和血小板开放小管系统的亲和力。血管萌芽的形成由对硫酸乙酰肝素具有最低亲和力的血管生成调节因子（例如 VEGF）触发，随后是对 HS 具有中等亲和力的血管稳定 PDGF-B 或 bFGF，以及对 HS 具有最高亲和力的抑制剂，如 PF-4 和 TSP-1。生长肿瘤的侵袭性伤口样边缘具有过量的血管生成刺激物，我们认为它们的丰富程度超过了血管生成抑制剂，有效地防止了血管生成和血管成熟的抑制。我们使用基于实验的基于代理的模型来评估这一假设，并提出了一个通用的理论框架，用于从竞争性抑制的角度理解正常伤口愈合和病理性血管生成过程之间的机制相似性和差异。
Both normal wound healing and tumor angiogenesis are mitigated by the sequential, carefully orchestrated release of growth stimulators and inhibitors. These regulators are released from platelet clots formed at the sites of activated endothelium in a temporally and spatially controlled manner, and the order of their release depends on their affinity to glycosaminoglycans (GAG) such as heparan sulfate (HS) within the extracellular matrix, and platelet open canallicular system. The formation of vessel sprouts, triggered by angiogenesis regulating factors with lowest affinities for heparan sulfate (e.g. VEGF), is followed by vessel-stabilizing PDGF-B or bFGF with medium affinity for HS, and by inhibitors such as PF-4 and TSP-1 with the highest affinities for HS. The invasive wound-like edge of growing tumors has an overabundance of angiogenesis stimulators, and we propose that their abundance out-competes angiogenesis inhibitors, effectively preventing inhibition of angiogenesis and vessel maturation. We evaluate this hypothesis using an experimentally motivated agent-based model, and propose a general theoretical framework for understanding mechanistic similarities and differences between the processes of normal wound healing and pathological angiogenesis from the point of view of competitive inhibition.
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影响因子：
14
作者：
Mehdizadeh, Hamidreza;Sumo, Sami;Cinar, Ali
通讯作者：
Cinar, Ali
DOI：
10.1073/pnas.82.3.805
发表时间：
1985-01-01
影响因子：
11.1
作者：
KLAGSBRUN, M;SHING, Y
通讯作者：
SHING, Y
影响因子：
5.4
作者：
Blanco, Raquel;Gerhardt, Holger
通讯作者：
Gerhardt, Holger
肿瘤微环境产生的酸度驱动局部侵袭。
影响因子：
11.2
作者：
Estrella V;Chen T;Lloyd M;Wojtkowiak J;Cornnell HH;Ibrahim-Hashim A;Bailey K;Balagurunathan Y;Rothberg JM;Sloane BF;Johnson J;Gatenby RA;Gillies RJ
通讯作者：
Gillies RJ
DOI：
10.1111/j.1538-7836.2009.03387.x
发表时间：
2009-07
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Italiano JE Jr;Battinelli EM
通讯作者：
Battinelli EM