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Nucleoside transport in normal and neoplastic cells
J A Belt1, N M Marina, D A Phelps
1Department of Biochemical and Clinical Pharmacology, St. Jude Children's Research Hospital, Memphis, TN 38101.
Advances in Enzyme Regulation
|January 1, 1993
Summary
Mammalian cells utilize multiple nucleoside transporters, with differing sensitivities to inhibitors. Targeting these transporters in tumors may offer new cancer chemotherapy strategies by exploiting differences between tumor and normal tissues.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Nucleoside transport across mammalian cell plasma membranes is complex, involving at least five distinct transporters.
- These transporters exhibit varied sensitivities to inhibitors and specificities for nucleosides.
- Potential differences in transporter distribution between tumors and normal tissues could be leveraged for cancer chemotherapy.
Purpose of the Study:
- To investigate the role of nucleoside transporters in mammalian cells.
- To explore the potential of targeting nucleoside transporters for cancer treatment.
- To analyze the differential expression of nucleoside transporters in tumor versus normal tissues.
Main Methods:
- Characterization of nucleoside transporter properties and permeant specificity.
- Examination of nucleoside transporter expression in human tumor cell lines and normal tissues.
- Assessment of transporter sensitivity to inhibitors like NBMPR and dipyridamole.
Main Results:
- Human tumor cell lines predominantly express the NBMPR-sensitive equilibrative transporter (es).
- Tumors lacking NBMPR-insensitive transport may be susceptible to combined therapy with transport and de novo pyrimidine synthesis inhibitors.
- Normal tissues like intestine and bone marrow possess Na(+)-dependent transporters, potentially offering protection from antimetabolite toxicity.
Conclusions:
- Exploiting differential nucleoside transporter expression presents a promising avenue for cancer chemotherapy.
- Therapeutic success may depend on identifying individual tumor nucleoside transport phenotypes.
- Future development of antibodies and cDNA probes will enable feasible analysis of tumor nucleoside transport from biopsy material.