Buckley N D, Carlsen S A
Department of Microbiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Cancer Res. 1988 Mar 15;48(6):1451-5.
Many human tumors, such as those of the breast, metastasize initially via the lymphatics. The tumor cell surface is believed to play a critical role in this process. To study the cell surface properties involved in dissemination, the poorly metastasizing R3230AC rat mammary adenocarcinoma was enriched for metastasizing cells by excising rare lymph node metastases arising after the s.c. injection of 10(6) cells and reinjecting these cells into another series of rats. By repeated enrichment cycles, the frequency of lymphatic metastasis was increased from 10 to 60-100% of the animals given injections. Fluorescein-conjugated lectins were used to probe the tumor cell surface. It was found that the percentage of cells in the population able to bind high levels of the lectin, soybean agglutinin (SBA), increased from 11 to almost 80% in the highly metastatic, enriched cell populations. A linear correlation (r = 0.92; P less than 0.001) was found between the percentage of cells in the population which bound high levels of SBA and the frequency of lymphatic metastasis in a series of enriched cell lines. Clones which bound high levels of SBA metastasized to lymph nodes at a high frequency, while clones which bound only low amounts of SBA exhibited a low frequency of lymphatic metastasis regardless of the metastatic potential of the cell line from which the clones were isolated. The binding of SBA to the cell was reduced by preincubation of the lectin with galactose, completely blocked by incubation with N-acetylgalactosamine, and unaffected by incubation with glucose or mannose, demonstrating that SBA was recognizing a N-acetylgalactosamine-containing component of the cell surface. Cells enriched for lymphatic metastasis were not similarly enriched for hematogenous metastasis. While cell lines enriched for lymphatic metastasis have been previously described, this is the first report of a specific cell surface property, SBA-binding, associated with lymphatic metastasis.
许多人类肿瘤，如乳腺癌，最初是通过淋巴管转移的。肿瘤细胞表面被认为在这一过程中起着关键作用。为了研究参与扩散的细胞表面特性，通过切除皮下注射10⁶个细胞后出现的罕见淋巴结转移灶，并将这些细胞重新注射到另一组大鼠体内，对转移能力较差的R3230AC大鼠乳腺腺癌进行转移细胞富集。通过重复富集循环，淋巴转移的频率从接受注射动物的10%增加到60 - 100%。用荧光素偶联的凝集素探测肿瘤细胞表面。发现在高转移性的富集细胞群体中，能够结合高水平凝集素大豆凝集素（SBA）的细胞百分比从11%增加到近80%。在一系列富集细胞系中，结合高水平SBA的细胞百分比与淋巴转移频率之间发现了线性相关性（r = 0.92；P < 0.001）。结合高水平SBA的克隆高频转移至淋巴结，而仅结合少量SBA的克隆无论其分离自何种细胞系的转移潜能如何，均表现出低频率的淋巴转移。用半乳糖预孵育凝集素可降低SBA与细胞的结合，用N - 乙酰半乳糖胺孵育可完全阻断结合，而用葡萄糖或甘露糖孵育则无影响，这表明SBA识别的是细胞表面含N - 乙酰半乳糖胺的成分。富集淋巴转移的细胞对于血行转移并没有类似的富集。虽然之前已经描述过富集淋巴转移的细胞系，但这是首次报道与淋巴转移相关的特定细胞表面特性——SBA结合。
