Wieser R J, Janik-Schmitt B, Renauer D, Schäfer A, Heck R, Oesch F
Institute of Toxicology, University of Mainz, F.R.G.
Biochimie. 1988 Nov;70(11):1661-71. doi: 10.1016/0300-9084(88)90301-x.
Homeostasis in vivo is maintained by a highly complex network of positive and negative signals. At the cellular level, this regulatory microenvironment can be divided, in a simplified fashion, into two major compartments: the humoral compartment, including compounds such as hormones, growth factors and nutrients, and the contact-environment compartment, including cell-cell and cell-matrix interactions. At least in cultures of diploid, non-transformed cells, cell-cell and cell-matrix interactions have been shown to be of major importance for the regulation of growth as well as of differentiation. Although until now the glycoprotein involved in the contact-dependent inhibition of growth has not been fully characterized, our studies give evidence for the involvement of a plasma membrane glycoprotein with an apparent molecular weight of approximately 80 kDa in the growth regulation of diploid human fibroblasts. The important characteristic of this glycoprotein is: the biologically active determinant resides in terminal, beta-glycosidically linked galactose residues on N-glycosidically linked glycans. From our studies, a receptor has to be postulated which, in addition to the galactose residues, has additional structural requirements for the specific binding of this glycoprotein, since other glycoproteins carrying terminal, beta-glycosidically linked galactose-residues are without biological activity. The postulated receptor is suggested to be defective in tumor cells, since these cells are no longer able to respond to cell-cell contacts with stopped proliferation, although they are able to inhibit growth of non-transformed cells. The inability of a tumor cell to recognize and to bind to the specific glycoprotein would result in a release from growth inhibition, leading to clonal growth of these cells. Further detailed studies on the structure and the regulation of the glycoprotein, as well as an attempt to isolate the postulated receptor, should lead to a better understanding of the complex pattern of growth regulation of normal cells.
体内的稳态是由一个高度复杂的正负信号网络维持的。在细胞水平上，这种调节性微环境可以简单地分为两个主要部分：体液部分，包括激素、生长因子和营养物质等化合物；以及接触环境部分，包括细胞间和细胞与基质的相互作用。至少在二倍体、未转化细胞的培养中，细胞间和细胞与基质的相互作用已被证明对生长和分化的调节至关重要。尽管到目前为止参与接触依赖性生长抑制的糖蛋白尚未完全表征，但我们的研究为一种表观分子量约为80 kDa的质膜糖蛋白参与二倍体人成纤维细胞的生长调节提供了证据。这种糖蛋白的重要特征是：生物活性决定簇位于N-糖苷连接聚糖上末端的β-糖苷连接半乳糖残基上。从我们的研究中推测，除了半乳糖残基外，还必须存在一种受体，该受体对这种糖蛋白的特异性结合有额外的结构要求，因为其他携带末端β-糖苷连接半乳糖残基的糖蛋白没有生物活性。推测肿瘤细胞中的这种受体存在缺陷，因为这些细胞虽然能够抑制未转化细胞的生长，但不再能够对细胞间接触做出停止增殖的反应。肿瘤细胞无法识别和结合特定糖蛋白会导致其从生长抑制中释放出来，从而导致这些细胞的克隆生长。对该糖蛋白的结构和调节进行进一步详细研究，以及尝试分离推测的受体，应该会有助于更好地理解正常细胞生长调节的复杂模式。
