Tsuruoka T, Azetaka M, Iizuka Y, Saito K, Inouye S, Hosokawa M, Kobayashi H
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Yokohama.
Jpn J Cancer Res. 1995 Nov;86(11):1080-5. doi: 10.1111/j.1349-7006.1995.tb03024.x.
We used the Boyden chamber system to investigate the mechanism by which the antimetastatic agent sodium D-glucaro-delta-lactam (ND2001) inhibits tumor cell invasion, and by establishing what ND2001 did not achieve, we were able to pinpoint the areas in which it was successful as an inhibitor. ND2001 did not inhibit cell adhesion of a highly metastatic B16 melanoma variant (the B16 variant) to the reconstituted basal membrane Matrigel, nor did it affect the production or activity of basal membrane-degrading type i.v. collagenase, but, in the Boyden chamber, ND2001 inhibited cell migration of the B16 variant toward a chemoattractant, laminin, on the lower surface of a Matrigel-free filter set (haptotaxis). Lewis lung carcinoma (3LL) cells that had been treated with ND2001 also exhibited hardly any haptotaxis, although the cells showed no alteration in behavior during cell adhesion to Matrigel. Since ND2001 did succeed in inhibiting the pulmonary metastases of the B16 variant and 3LL, we infer that inhibition of the metastases by ND2001 in these tumors is likely to be due to the inhibition of haptotactic migration.
我们使用博伊登小室系统来研究抗转移剂D-葡萄糖醛酸-δ-内酯钠（ND2001）抑制肿瘤细胞侵袭的机制。通过明确ND2001未能达成的效果，我们得以精准定位其作为抑制剂取得成功的领域。ND2001既不抑制高转移性B16黑色素瘤变体（B16变体）与重组基底膜基质胶的细胞黏附，也不影响基底膜降解性IV型胶原酶的产生或活性。但是，在博伊登小室中，ND2001抑制了B16变体在不含基质胶的滤膜下表面朝着趋化因子层粘连蛋白的细胞迁移（趋触性）。用ND2001处理过的刘易斯肺癌（3LL）细胞也几乎没有表现出趋触性，尽管这些细胞在与基质胶黏附过程中的行为没有改变。由于ND2001确实成功抑制了B16变体和3LL的肺转移，我们推断ND2001对这些肿瘤转移的抑制作用可能归因于对趋触性迁移的抑制。
