Aeed P A, Nakajima M, Welch D R
Department of Cancer and Infectious Diseases Research, Upjohn Company, Kalamazoo, MI.
Int J Cancer. 1988 Nov 15;42(5):748-59. doi: 10.1002/ijc.2910420521.
Circulating neutrophil (PMN) levels can increase in rats bearing subcutaneously growing clones of the 13762NF mammary adenocarcinoma and the level of increase correlates with the metastatic potential of the clone. In rats with poorly metastatic MTC tumors, numbers of circulating PMN did not rise, whereas PMN levels rose 50-fold in rats bearing highly metastatic MTLn3, 12-fold in rats with weakly metastatic MTLn2, and 14-fold in those with moderately metastatic MTF7 tumors. Neutrophilia was caused partly by tumor size, but metastatic potential was a stronger determinant, suggesting that PMNs may play a role in the metastatic process. To determine whether circulating PMNs indeed contribute to cellular metastatic potential, we examined effects of PMN on various aspects of the metastatic process. Experimental metastasis assays involving i.v. co-injections of PMNs yielded a dose-dependent increase in extrapulmonary metastases for MTLn3, but no change in lung colonization potential for any of the clones examined. The change in the metastatic profile was not due to any modification in in vivo distribution of i.v. injected tumor cells or in adhesion to endothelial monolayers in vitro. PMNs also had no effect on in vitro DNA, RNA or protein synthesis and were not cytolytic (E:T 100:1). However, PMNs collected from high-passage MTLn3 tumor-bearing rats had a 50% increase in heparanase and type-IV collagenolytic activity as compared to unstimulated PMNs isolated from normal rats. These results indicate that polymorphonuclear cells may contribute to the metastatic potential of highly metastatic clones from the 13762NF mammary adenocarcinoma cells by assisting in the degradation of basement membrane during extravasation.
皮下接种13762NF乳腺腺癌克隆的大鼠，其循环中性粒细胞（PMN）水平会升高，且升高水平与克隆的转移潜能相关。在转移能力较差的MTC肿瘤大鼠中，循环PMN数量未增加，而在携带高转移潜能MTLn3的大鼠中，PMN水平升高了50倍，在低转移潜能MTLn2的大鼠中升高了12倍，在中转移潜能MTF7肿瘤大鼠中升高了14倍。中性粒细胞增多部分是由肿瘤大小引起的，但转移潜能是更强的决定因素，这表明PMN可能在转移过程中发挥作用。为了确定循环PMN是否确实有助于细胞的转移潜能，我们研究了PMN对转移过程各个方面的影响。涉及静脉共同注射PMN的实验性转移试验显示，MTLn3的肺外转移呈剂量依赖性增加，但在所检测的任何克隆中，肺定植潜能均无变化。转移谱的变化并非由于静脉注射肿瘤细胞在体内分布的任何改变或体外对内皮单层的黏附改变所致。PMN对体外DNA、RNA或蛋白质合成也没有影响，且无细胞溶解作用（效靶比为100:1）。然而，与从正常大鼠分离的未刺激PMN相比，从高传代MTLn3荷瘤大鼠收集的PMN的乙酰肝素酶和IV型胶原酶活性增加了50%。这些结果表明，多形核细胞可能通过在渗出过程中协助基底膜降解，从而有助于13762NF乳腺腺癌细胞高转移克隆的转移潜能。
