Linoleic acid metabolism in metastatic and nonmetastatic murine mammary tumor cells

R. S. Chapkin, Neil Hubbard, D. K. Buckman, Kent L Erickson

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The mechanism(s) by which dietary linoleic acid (18:2n-6) enhances mammary tumor growth and metastasis is not known. Since arachidonic acid (20:4n-6)-derived prostaglandins (PG) may play a role in the metastatic dissemination of tumor cells, the ability of two murine mammary tumor cell lines, 4526 (metastasis positive) and line 168 (spontaneous metastasis negative), to convert 18:2n-6 into prostaglandins was examined. Cells were initially incubated with [14C]18:2n-6 and after 8-24 h the [14C]fatty acids were quantitated by high-performance liquid chromatography following transesterification. [14C]18:2n-6 was metabolized primarily to [14C]dihomogammalinolenic acid (20:3n-6) in line 4526 cells and [14C]20:4n-6 in line 168 cells. Examination of cellular fatty acid levels revealed a 20:3n-6/20:4n-6 ratio of 1.79 ± 0.36 and 0.20 ± 0.02 in line 4526 and 168 cells, respectively. These data are consistent with an inherently lower Δ5 desaturase activity in line 4526 relative to 168. To assess the metabolism of 18:2n-6 into eicosanoid products, the cell lines were prelabeled with [14C]18:2n-6 or 0-40 μM nonradiolabeled 18:2n-6 overnight and subsequently stimulated with calcium ionophore A23187 for 1 h. Total PGE production, as determined by radioimmunoassay, was greater in 168 relative to 4526 cells at all 18:2n-6 concentrations. 14C-prostaglandins detected by high-performance liquid chromatography and argentation thin-layer chromatography were: PGF(1α) and PGE1 (derived from 20:3n-6) and PGF(2α) and PGE2 (derived from 20:4n-6) from line 4526; PGE1 and PGE2 from line 168. PGE1/PGE2 ratios were 1.43 ± 0.07 and 0.23 ± 0.03 for 4526 and 168 lines, respectively. Neither cell line synthesized lipoxygenase products following [14C]18:2n-6 or [3H]20:4n-6 incubations under the conditions employed. Additional studies are warranted in order to define the biological properties of 1- and 2- series cyclooxygenase products as they relate to tumor cell metastasis.

Original languageEnglish (US)
Pages (from-to)4724-4728
Number of pages5
JournalCancer Research
Volume49
Issue number17
StatePublished - 1989

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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