Inhibition of tumor cell haptotaxis by sodium D-glucaro-delta-lactam (ND2001).
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.
Tsuruoka
T
T
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Yokohama.
Azetaka
M
M
Iizuka
Y
Y
Saito
K
K
Inouye
S
S
Hosokawa
M
M
Kobayashi
H
H
D000230:Adenocarcinoma / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018287:Carcinoma, Large Cell / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D003094:Collagen; D017364:Collagenases / Q000032:analysis; D003864:Depression, Chemical; D004338:Drug Combinations; D005260:Female; D005937:Glucaric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007797:Laminin; D008175:Lung Neoplasms / Q000473:pathology; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000032:analysis; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000502:physiology; D010051:Ovarian Neoplasms / Q000473:pathology; D011509:Proteoglycans; D014407:Tumor Cells, Cultured / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000473:pathology
D000970:Antineoplastic Agents; D004338:Drug Combinations; D007797:Laminin; D009363:Neoplasm Proteins; D011509:Proteoglycans; C059485:matrigel; C001845:D-glucaro-delta-lactam; D003094:Collagen; D017364:Collagenases; D005937:Glucaric Acid