Brodt P, Fallavollita L, Sawka R J, Shibata P, Nip J, Kim U, Shibata H
Department of Surgery, McGill University, Montreal, Quebec, Canada.
Breast Cancer Res Treat. 1990 Dec;17(2):109-20. doi: 10.1007/BF01806291.
The role of tumor cell adhesion in lymphatic metastasis of breast cancer was investigated in vitro using a rat mammary carcinoma model of four cell lines with different metastatic phenotypes, two human breast cancer cell lines, and cryostast sections of normal rat or human lymph nodes, respectively. A positive correlation was found between the adhesion levels obtained with three metastatic rat mammary cell lines (TMT-081 greater than MT-100M & TMT-50) and a non-metastatic line MT-W9B, the latter being 3-4 fold less adhesive to the lymph node sections than the metastatic tumors. This selective adhesion was specific, as it was not found with cryostat sections of rat liver and brain. Enzyme assays indicated that cell surface glycoproteins bearing terminal beta-galactoside residues were involved in the adhesion of the rat tumors. Adhesion of the human breast carcinoma cells Hs578T to sections of human lymph nodes was significantly higher than that of the normal breast epithelial cell line Hs578Bst, and comparable to adhesion of a second breast carcinoma line, MCF-7. Moreover, Hs578T cells isolated from regional lymph nodes of tumor-bearing nude mice were significantly more adhesive to human lymph node sections than the parental line. Adhesion of both human and rat tumors could be partially blocked by the addition of the synthetic peptide GRGDSPK and by antibodies directed to the beta 1 chain of integrin, suggesting that an integrin receptor may played a role in the adhesion. The results suggest that tumor cell adhesion to cryostat sections of lymph nodes is a correlate of the malignant phenotype in mammary tumors of diverse origins, and could be used to delineate the adhesion factors mediating lymphatic metastasis.
利用具有不同转移表型的四种细胞系的大鼠乳腺癌模型、两种人乳腺癌细胞系,以及分别来自正常大鼠或人淋巴结的冷冻切片,在体外研究了肿瘤细胞黏附在乳腺癌淋巴转移中的作用。在三种转移性大鼠乳腺细胞系(TMT-081大于MT-100M和TMT-50)与非转移性细胞系MT-W9B之间发现了黏附水平的正相关,后者对淋巴结切片的黏附性比转移性肿瘤低3至4倍。这种选择性黏附是特异性的,因为在大鼠肝脏和脑的冷冻切片中未发现。酶分析表明,带有末端β-半乳糖苷残基的细胞表面糖蛋白参与了大鼠肿瘤的黏附。人乳腺癌细胞Hs578T对人淋巴结切片的黏附性明显高于正常乳腺上皮细胞系Hs578Bst,与另一种乳腺癌细胞系MCF-7的黏附性相当。此外,从荷瘤裸鼠区域淋巴结分离的Hs578T细胞对人淋巴结切片的黏附性明显高于亲代细胞系。添加合成肽GRGDSPK和针对整合素β1链的抗体可部分阻断人和大鼠肿瘤的黏附,表明整合素受体可能在黏附中起作用。结果表明,肿瘤细胞对淋巴结冷冻切片的黏附是不同来源乳腺肿瘤恶性表型的一个相关因素,可用于确定介导淋巴转移的黏附因子。