Zeng C, Toole B P, Kinney S D, Kuo J W, Stamenkovic I
Department of Pathology, Harvard Medical School, and Pathology Research Laboratories, Massachusetts General Hospital, Boston 02129, USA.
Int J Cancer. 1998 Jul 29;77(3):396-401. doi: 10.1002/(sici)1097-0215(19980729)77:3<396::aid-ijc15>3.0.co;2-6.
One of the critical events in tumor growth and metastasis is the interaction between tumor cells and host tissue stroma, mediated by different adhesion receptor repertoires in different tumor cell types. Several lines of evidence indicate that interaction between the hyaluronan receptor CD44, expressed on tumor cells, and host tissue stromal hyaluronan can enhance growth and invasiveness of certain tumors. Disruption of CD44-hyaluronan interaction by soluble recombinant CD44 has been shown to inhibit tumor formation by lymphoma and melanoma cells transfected with CD44. Since hyaluronan is a ubiquitous glycosaminoglycan polymer from which oligosaccharides of defined size can be readily purified, we tested the ability of hyaluronan oligomers to inhibit tumor formation by subcutaneously (s.c.) injected B16F10 melanoma cells. Our results indicate that hyaluronan oligomers injected at concentrations as low as 1 mg/ml can markedly inhibit B16F10 melanoma growth, providing a potentially attractive reagent for the control of local tumor development.
肿瘤生长和转移过程中的关键事件之一是肿瘤细胞与宿主组织基质之间的相互作用,这一过程由不同肿瘤细胞类型中不同的黏附受体库介导。多项证据表明,肿瘤细胞上表达的透明质酸受体CD44与宿主组织基质透明质酸之间的相互作用可增强某些肿瘤的生长和侵袭性。可溶性重组CD44破坏CD44-透明质酸的相互作用已被证明可抑制转染了CD44的淋巴瘤和黑色素瘤细胞形成肿瘤。由于透明质酸是一种普遍存在的糖胺聚糖聚合物,从中可以很容易地纯化出特定大小的寡糖,因此我们测试了透明质酸寡聚物抑制皮下注射B16F10黑色素瘤细胞形成肿瘤的能力。我们的结果表明,浓度低至1 mg/ml的透明质酸寡聚物注射可显著抑制B16F10黑色素瘤的生长,为控制局部肿瘤发展提供了一种潜在有吸引力的试剂。