Dp. Rose et Jm. Connolly, DIETARY-FAT AND BREAST-CANCER METASTASIS BY HUMAN TUMOR XENOGRAFTS, Breast cancer research and treatment, 46(2-3), 1997, pp. 225-237
Human breast cancer cell Lines growing as xenografts in athymic nude m
ice have been used to examine the effects of dietary fat and fatty aci
ds on tumor progression. The estrogen independent MDA-MB-435 cell line
has the advantage that it metastasizes consistently to the lungs and
forms quantifiable secondary nodules when injected into the mammary fa
t pads. With these breast cancer cells, the stimulating effects of pol
yunsaturated omega-6 fatty acids on both primary tumor growth and meta
stasis were demonstrated; in contrast, the long-chain omega-3 fatty ac
ids were inhibitory. The model can also be adapted to examine dietary
fatty acids, and inhibitors of their metabolism, as experimental adjuv
ant therapy after surgical excision of the primary tumors. Unfortunate
ly, estrogen dependent human breast cancer cells do not metastasize, o
r do so rarely, in nude mice; in consequence, it is not possible to us
e the model to study estrogen-fatty acid interactions on the metastati
c process. In addition to metastasis from a primary location, intraven
ous injection of MDA-MB-435 cells into the nude mouse host, particular
ly when combined with studies using Matrigel-based in vitro invasion a
ssays, permits further dissection of the steps in the metastatic casca
de which are influenced by dietary fatty acids. The results obtained b
y these several approaches have demonstrated distinct roles for the cy
clooxygenase and lipoxygenase-mediated products of omega-6 fatty acid
metabolism, and suggest new approaches to experimental breast cancer t
herapy.