Yamamura K, Kibbey M C, Kleinman H K
Laboratory of Developmental Biology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
Cancer Res. 1993 Jan 15;53(2):423-8.
Laminin is an important promoter of cell-matrix interactions. A number of active laminin domains have been defined by use of synthetic peptides. The Tyr-Ile-Gly-Ser-Arg (YIGSR) sequence on the B1 chain in laminin can decrease tumor growth and metastasis, whereas another sequence containing Ser-Ile-Lys-Val-Ala-Val (SIKVAV) on the A chain can increase tumor growth and metastasis. Here, we selected B16-F10 melanoma cells by adherence or nonadherence to either YIGSR- or SIKVAV-coated dishes and established 3 B16-F10 variants: YIGSR-adherent cells (Y+), YIGSR-nonadherent cells (Y-), and SIKVAV-nonadherent cells (S-). SIKVAV-adherent cells were not selected because most of F10 cells attached to the SIKVAV-coated dish. These cell lines proliferated at the same rate as the parent F10 cells and attached equally to laminin, collagen IV, and fibronectin. Y+ cells produced rapidly growing tumors after s.c. injection and twice as many lung colonies as the parental F10 cells after i.v. injection. In contrast, Y- cells produced more slowly growing tumors after s.c. injection and produced one-third of the lung colonies relative to the parent cells after i.v. injection. S- cells produced slowly growing tumors after s.c. injection and yielded similar numbers but smaller colonies in the lung than the parental B16-F10 cells after i.v. injection. These data suggest that interactions of melanoma cells with the YIGSR site on laminin are probably important for both colony formation in a target organ (lung) and subsequent tumor growth, while the SIKVAV-containing site on laminin may be more important for tumor growth.
层粘连蛋白是细胞与基质相互作用的重要促进因子。通过使用合成肽已确定了许多层粘连蛋白的活性结构域。层粘连蛋白B1链上的酪氨酸 - 异亮氨酸 - 甘氨酸 - 丝氨酸 - 精氨酸（YIGSR）序列可减少肿瘤生长和转移，而A链上另一个包含丝氨酸 - 异亮氨酸 - 赖氨酸 - 缬氨酸 - 丙氨酸 - 缬氨酸（SIKVAV）的序列则可增加肿瘤生长和转移。在此，我们通过将B16 - F10黑色素瘤细胞接种于包被有YIGSR或SIKVAV的培养皿上，根据细胞的黏附或不黏附情况筛选出3种B16 - F10变体：YIGSR黏附细胞（Y +）、YIGSR不黏附细胞（Y -）和SIKVAV不黏附细胞（S -）。未筛选SIKVAV黏附细胞，因为大多数F10细胞都附着在包被有SIKVAV的培养皿上。这些细胞系的增殖速度与亲本F10细胞相同，并且对层粘连蛋白、IV型胶原和纤连蛋白的黏附能力相同。皮下注射后，Y +细胞产生快速生长的肿瘤，静脉注射后肺部菌落数量是亲本F10细胞的两倍。相比之下，皮下注射后Y -细胞产生生长较慢的肿瘤，静脉注射后肺部菌落数量仅为亲本细胞的三分之一。皮下注射后，S -细胞产生生长缓慢的肿瘤，静脉注射后肺部菌落数量与亲本B16 - F10细胞相似，但菌落较小。这些数据表明，黑色素瘤细胞与层粘连蛋白上YIGSR位点的相互作用可能对靶器官（肺）中的菌落形成和随后的肿瘤生长都很重要，而层粘连蛋白上含SIKVAV的位点可能对肿瘤生长更为重要。
