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.
authors.affiliation: Department of Nutritional Sciences, Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Qiuyan
authors.initials: Q
authors.lastname: Chen
authors.forename: A Catharine
authors.initials: AC
authors.lastname: Ross
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage*; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology / Q000556:secondary*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000517:prevention & control*; D053511:Matrix Metalloproteinase 14 / Q000032:analysis; D019278:Matrix Metalloproteinase 3 / Q000032:analysis / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000473:pathology / Q000517:prevention & control; D009368:Neoplasm Transplantation; D014212:Tretinoin / Q000008:administration & dosage*
chemical_list: D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D014212:Tretinoin; D019278:Matrix Metalloproteinase 3; D053511:Matrix Metalloproteinase 14