A new anti-metastatic drug, ND-2001, inhibits lung metastases in rat hepatoma cells by suppressing haptotaxis of tumor cells toward laminin.
We examined the effects of ex vivo treatment of tumor cells with sodium D-glucaro-delta-lactam (sodium 5-amino-5-deoxy-D-glucosaccharic acid-delta-lactam; ND-2001). The ex vivo treatment of rat hepatoma cKDH-8/11 cells with this new synthetic product of the antibiotic nojirimycin, ND-2001 (50 microg/ml), inhibited the experimentally induced lung metastases of the tumor cells significantly at an inhibition rate of 69.2% (one of 10 animals remained metastasis free). Also, it was elucidated in in vitro tumor cell invasion assays that ND-2001 (50 microg/ml) suppressed the invasion activities of cKDH-8/11 cells to Matrigel Matrix at an inhibition rate of 69.3%. However, phagokinetic track assays revealed that ND-2001 did not suppress the random motility of cKDH-8/11 cells. However, ND-2001 (50 microg/ml) suppressed the haptotaxis, another important role in tumor invasion, of cKDH-8/11 cells toward laminin (inhibition rate of 77.0%). These results suggest that ND-2001 suppressed the haptotaxis of tumor cells toward laminin directly at the step of invading the basement membrane and brought about the inhibition of lung metastases.
Kuramitsu
Y
Y
Laboratory of Pathology, Cancer Institute, Hokkaido University School of Medicine, Kita, Sapporo, Japan.
Hamada
J
J
Tsuruoka
T
T
Morikawa
K
K
Kobayashi
H
H
Hosokawa
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D005260:Female; D005937:Glucaric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D007797:Laminin / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000473:pathology*; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary*; D009362:Neoplasm Metastasis; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D007797:Laminin; C001845:D-glucaro-delta-lactam; D005937:Glucaric Acid