Satoh M, Handa K, Saito S, Tokuyama S, Ito A, Miyao N, Orikasa S, Hakomori S
Department of Urology, Tohoku University School of Medicine, Sendai, Japan.
Cancer Res. 1996 Apr 15;56(8):1932-8.
Aberrant glycosylation expressed in specific types of human cancer may define stage, direction, and fate of tumor progression. Well-studied examples are expression of sialosyl-Lewis(x) or sialosyl-Lewis(a) in colorectal carcinoma and histo-blood group A and H/Le(y) in lung cancer. In renal cell carcinoma (RCC), expression of sialosyl-Lewis(x) has no correlation with metastatic potential. Clinicopathological studies have revealed that the degree of expression of disialosyl galactosylgloboside (DSGG) and monosialosyl galactosylgloboside is correlated with metastatic potential (to lung and lymph nodes) of RCC and inversely correlated with patient survival. In the present study, we compared the adhesion of RCC lines to sections of various tissues measured by Stamper-Woodruff assay and other similar assays under dynamic flow conditions. Of the eight RCC lines tested, only TOS-1 (which expresses DSGG) bound strongly to lung tissue sections. TOS-1 did not bind to sections of liver, kidney, or lymph nodes. In the same eight RCC lines, we also compared expression of DSGG and monosialosyl galactosylgloboside (reflected by reactivity with RM1 and RM2), overall ganglioside patterns, and correlation with lung tissue-binding ability. Under both static and dynamic flow conditions, the binding of TOS-1 cells to lung alveolar tissue was correlated with their DSGG expression, i.e., the binding was inhibited by RM2 but not by RM1. This binding was also inhibited by sialidase but not by EDTA (i.e., it was CA 2+ independent). The other seven cell lines (TOS-2, TOS-M, SMKT-R1, -R2, -R3, and -R4, and ACHN), which do not express DSGG, showed much weaker adhesion to lung tissue. None of the eight cell lines showed E- or P-selectin-dependent adhesion. These results suggest the existence of a yet-uncharacterized sialoadhesive receptor++ that specifically recognizes DSGG. This receptor could be the binding target in RCC metastasis to lung.
在特定类型的人类癌症中表达的异常糖基化可能决定肿瘤进展的阶段、方向和命运。研究充分的例子包括结直肠癌中唾液酸化刘易斯（x）或唾液酸化刘易斯（a）的表达，以及肺癌中组织血型A和H/Le（y）的表达。在肾细胞癌（RCC）中，唾液酸化刘易斯（x）的表达与转移潜能无关。临床病理研究表明，二唾液酸化半乳糖神经节苷脂（DSGG）和单唾液酸化半乳糖神经节苷脂的表达程度与RCC的转移潜能（至肺和淋巴结）相关，与患者生存率呈负相关。在本研究中，我们比较了RCC细胞系在动态流动条件下通过Stamper-Woodruff试验和其他类似试验测量的与各种组织切片的黏附情况。在测试的8个RCC细胞系中，只有TOS-1（表达DSGG）与肺组织切片强烈结合。TOS-1不与肝、肾或淋巴结切片结合。在同样的8个RCC细胞系中，我们还比较了DSGG和单唾液酸化半乳糖神经节苷脂的表达（通过与RM1和RM2的反应性反映）、总体神经节苷脂模式以及与肺组织结合能力的相关性。在静态和动态流动条件下，TOS-1细胞与肺泡组织的结合都与其DSGG表达相关，即这种结合被RM2抑制，但不被RM1抑制。这种结合也被唾液酸酶抑制，但不被EDTA抑制（即它不依赖Ca²⁺）。其他7个不表达DSGG的细胞系（TOS-2、TOS-M、SMKT-R1、-R2、-R3、-R4和ACHN）对肺组织的黏附力弱得多。这8个细胞系均未表现出E或P选择素依赖性黏附。这些结果表明存在一种尚未明确特征的唾液酸黏附受体++，它能特异性识别DSGG。该受体可能是RCC转移至肺的结合靶点。
