Hierarchy of stroma-derived factors in supporting growth of stroma-dependent hemopoietic cells:: Membrane-bound SCF is sufficient to confer stroma competence to epithelial cells
Hierarchy of stroma-derived factors in supporting growth of stroma-dependent hemopoietic cells:: Membrane-bound SCF is sufficient to confer stroma competence to epithelial cells
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DOI：
10.1080/08977190290022211
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发表时间：
2002-03-01
期刊：
影响因子：
1.8
通讯作者：
Ostertag, W
中科院分区：
文献类型：
--
作者：
Friel, J;Itoh, K;Ostertag, W
造血发生在造血细胞通过各种相互作用与基质密切相关的微环境中。间质协同调节造血细胞的增殖和分化。基质-造血细胞接触可由局部产生的膜相关生长因子支持。基质源性生长因子（stroma-derivedgrowthfactor，SCF）在造血过程中起重要作用.我们研究了膜结合和可溶性SCF与表达SCF受体c-kit的人造血细胞的不同生物学相互作用。为了分析SCF同种型在诱导造血TF 1或脐带血（CB）CD 34（+）细胞增殖中的功能，我们使用了基质细胞，这些细胞系在无SCF、膜SCF或可溶性SCF的表达方面不同。我们建立了一个新的共培养系统，使用上皮细胞系，排除潜在的干扰作用与其他已知的基质编码造血生长因子。我们发现，可溶性SCF，在膜结合SCF的情况下，抑制长期的克隆生长的主要或建立的CD 34+造血细胞，而膜插入SCF“占主导地位”诱导这些细胞的长期增殖。我们证明了这些SCF亚型在基质与造血TF 1细胞的相互作用中的层次结构。膜结合的SCF是“显性”的可溶性SCF，而可溶性SCF的行为上位性与造血细胞的相互作用相比，其他基质衍生因子存在于SCF缺乏基质。间质细胞系的层次结构可以根据它们的膜SCF或可溶性SCE的呈现来排列。在我们的模型系统中，膜结合SCF表达足以赋予上皮细胞系间质性质，但可溶性SCF不。
Hemopoiesis takes place in a microenvironment where hemopoietic cells are closely associated with stroma by various interactions. Stroma coregulates the proliferation and differentiation of hemopoietic cells. Stroma-hemopoietic-cell contact can be supported by locally produced membrane associated growth factors. The stroma derived growth factor, stem cell factor (SCF) is important in hemopoiesis. We examined the different biological interactions of membrane bound and soluble SCF with human hemopoietic cells expressing the SCF receptor, c-kit. To analyze the function of the SCF isoforms in inducing the proliferation of hemopoietic TF1 or Cord blood (CB) CD34(+) cells we used stroma, cell lines that differ in their presentation of no SCF, membrane SCF, or soluble SCF. We established a new coculture system using an epithelial cell line that excludes potential interfering effects with other known stroma encoded hemopoietic growth factors. We show that soluble SCF, in absence of membrane-bound SCF, inhibits long term clonal growth of primary or established CD34+ hemopoietic cells, whereas membrane-inserted SCF "dominantly" induces long term proliferation of these cells. We demonstrate a hierarchy of these SCF isoforms in the interaction of stroma with hemopoietic TF1 cells. Membrane-bound SCF is "dominant" over soluble SCF, whereas soluble SCF acts epistatically in interacting with hemopoietic cells compared with other stroma derived factors present in SCF deficient stroma. A hierarchy of stroma cell lines can be arranged according to their presentation of membrane SCF or soluble SCE In our model system, membrane-bound SCF expression is sufficient to confer stroma properties to an epithelial cell line but soluble SCF does not.