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Selective inhibition of spontaneous pulmonary metastasis of lewis lung carcinoma by 5′‐deoxy‐5‐fluorouridine
Author(s) -
Ishikawa Tohru,
Ura Masako,
Yamamoto Taeko,
Tanaka Yutaka,
Ishitsuka Hideo
Publication year - 1995
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910610415
Subject(s) - lewis lung carcinoma , metastasis , cancer research , collagenase , carcinoma , lung , tumor necrosis factor alpha , medicine , primary tumor , pathology , biology , immunology , cancer , biochemistry , enzyme
5′‐deoxy‐5‐fluorouridine (5′‐FUdR) is a cytostatic that is biotransformed to 5‐fluorouracil (5‐FUra) by pyrimidine nucleo‐side phosphorylase (PyNPase), the expression of which is up‐regulated by tumor necrosis factor α (TNFα), interleukin‐1 α (IL‐1α) and interferon γ (IFNγ). In Lewis lung carcinoma (LLC) cell cultures, these inflammatory cytokines up‐regulated the expression of type‐IV collagenase, a metastatic factor, as well as PyNPase and consequently enhanced the antiproliferative activity of 5′‐FUdR. However, the activity of 5‐FUra was not enhanced. It appears that 5′‐FUdR selectively kills highly metastatic cells which are exposed to these intrinsic cytokines in tumor tissues, because of their high PyNPase activity. In fact, 5′‐FUdR inhibited the spontaneous metastasis of LLC from the s.c. inoculation site to the lung. When 5′‐FUdR was given during the process of metastasis, it greatly reduced the number of tumor nodules in the lung even at doses 46 times lower than those inhibiting the primary tumor growth. In addition, 5′‐FUdR, but not 5‐FUra, lowered type‐IV collagenase levels in the tumors at the low dose showing only anti‐metastatic activity. On the other hand, 5‐FUra showed anti‐metastatic activity at doses similar to or only several times lower than those inhibiting the primary tumor growth. © 1995 Wiley‐Liss, Inc .