All-trans-retinoic acid and the glycolipid α-galactosylceramide combined reduce breast tumor growth and lung metastasis in a 4T1 murine breast tumor model

Qiuyan Chen, A. Catharine Ross

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Vitamin A compounds are promising for cancer prevention and reducing risk of recurrence. Herein we have evaluated the combination of all-trans-retinoic acid (RA), a vitamin A metabolite, and alpha-galactosylceramide (αGalCer), a lipid immune activator, in Balb/C mice inoculated with syngeneic 4T1 breast tumor cells on reduction in breast tumor growth and lung metastasis. In Balb/c inoculated with the syngenic 4T1 primary tumor, and administered dendritic cells treated with RA + αGalCer, the size of the primary tumor and the number of lung metastatic foci were reduced. When 4T1 cells were introduced into the circulation as a model of hematogenous spread of tumor cells and RA and αCalCer were administered directly to mice without dendritic cells, lung metastatic foci were reduced 70% (P < 0.05), whereas each agent alone resulted in an intermediate decrease. Concomitantly, the expression of matrix metalloproteinases (MMP), membrane type-1 (MT1)-MMP and MMP3, were reduced by RA + αGalCer in lung. MMP3 protein was also reduced in plasma and culture supernatants from RA + αGalCer-treated 4T1 cells. Together, our results provide new evidence that a nutritional-immunological combination of RA + αGalCer may be promising for preventing or slowing the growth of metastatic foci, and suggest reduced MMP production as a possible mechanism.

Original languageEnglish (US)
Pages (from-to)1219-1227
Number of pages9
JournalNutrition and cancer
Volume64
Issue number8
DOIs
StatePublished - Dec 1 2012

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Galactosylceramides
Glycolipids
Tretinoin
Breast Neoplasms
Neoplasm Metastasis
Lung
Growth
Matrix Metalloproteinases
Vitamin A
Dendritic Cells
Neoplasms
Matrix Metalloproteinase 14
Lipids
Recurrence

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Oncology
  • Nutrition and Dietetics
  • Cancer Research

Cite this

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title = "All-trans-retinoic acid and the glycolipid α-galactosylceramide combined reduce breast tumor growth and lung metastasis in a 4T1 murine breast tumor model",
abstract = "Vitamin A compounds are promising for cancer prevention and reducing risk of recurrence. Herein we have evaluated the combination of all-trans-retinoic acid (RA), a vitamin A metabolite, and alpha-galactosylceramide (αGalCer), a lipid immune activator, in Balb/C mice inoculated with syngeneic 4T1 breast tumor cells on reduction in breast tumor growth and lung metastasis. In Balb/c inoculated with the syngenic 4T1 primary tumor, and administered dendritic cells treated with RA + αGalCer, the size of the primary tumor and the number of lung metastatic foci were reduced. When 4T1 cells were introduced into the circulation as a model of hematogenous spread of tumor cells and RA and αCalCer were administered directly to mice without dendritic cells, lung metastatic foci were reduced 70{\%} (P < 0.05), whereas each agent alone resulted in an intermediate decrease. Concomitantly, the expression of matrix metalloproteinases (MMP), membrane type-1 (MT1)-MMP and MMP3, were reduced by RA + αGalCer in lung. MMP3 protein was also reduced in plasma and culture supernatants from RA + αGalCer-treated 4T1 cells. Together, our results provide new evidence that a nutritional-immunological combination of RA + αGalCer may be promising for preventing or slowing the growth of metastatic foci, and suggest reduced MMP production as a possible mechanism.",
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