Faculty Collaboration Database

Fatty acid metabolites in rapidly proliferating breast cancer. PLoS One 2013;8(5):e63076

Date

05/10/2013

Pubmed ID

23658799

Pubmed Central ID

PMC3642080

DOI

10.1371/journal.pone.0063076

Scopus ID

2-s2.0-84877021616 (requires institutional sign-in at Scopus site)   32 Citations

Abstract

PURPOSE: Breast cancers that over-express a lipoxygenase or cyclooxygenase are associated with poor survival possibly because they overproduce metabolites that alter the cancer's malignant behaviors. However, these metabolites and behaviors have not been identified. We here identify which metabolites among those that stimulate breast cancer cell proliferation in vitro are associated with rapidly proliferating breast cancer.

EXPERIMENTAL DESIGN: We used selective ion monitoring-mass spectrometry to quantify in the cancer and normal breast tissue of 27 patients metabolites that stimulate (15-, 12-, 5-hydroxy-, and 5-oxo-eicosatetraenoate, 13-hydroxy-octadecaenoate [HODE]) or inhibit (prostaglandin [PG]E2 and D2) breast cancer cell proliferation. We then related their levels to each cancer's proliferation rate as defined by its Mib1 score.

RESULTS: 13-HODE was the only metabolite strongly, significantly, and positively associated with Mib1 scores. It was similarly associated with aggressive grade and a key component of grade, mitosis, and also trended to be associated with lymph node metastasis. PGE2 and PGD2 trended to be negatively associated with these markers. No other metabolite in cancer and no metabolite in normal tissue had this profile of associations.

CONCLUSIONS: Our data fit a model wherein the overproduction of 13-HODE by 15-lipoxygenase-1 shortens breast cancer survival by stimulating its cells to proliferate and possibly metastasize; no other oxygenase-metabolite pathway, including cyclooxygenase-PGE2/D2 pathways, uses this specific mechanism to shorten survival.

Author List

O'Flaherty JT, Wooten RE, Samuel MP, Thomas MJ, Levine EA, Case LD, Akman SA, Edwards IJ

MESH terms used to index this publication - Major topics in bold

Biomarkers, Tumor
Breast Neoplasms
Cell Line, Tumor
Cell Proliferation
Fatty Acids
Humans
Middle Aged
Neoplasm Grading
Neoplasm Metastasis