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Anticopper
treatment inhibits pseudopodial protrusion and the invasive spread of 9L
gliosarcoma cells in the rat brain
Brem S, Tsanaclis AM,
Zagzag D
Lady
Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General
Hospital, Department of Neurology and Neurosurgery, Montreal, Quebec, Canada
The copper ion, a cofactor of angiogenesis, is sequestered in human brain tumors
and the adjacent brain.
The invasive spread of neoplastic cells has been linked to angiogenesis and
involves similar mechanisms of migration and tumor-matrix interaction.
In this report, copper depletion inhibited the infiltrative spread of the
normally invasive 9L gliosarcoma.
Twenty made Fischer 344 rats were each injected with 1 X 10(5) 9L cells; 10 rats
were treated with a low-copper diet and penicillamine.
In the normocupremic control rats, a "diffuse" invasive pattern was
observed in all 10 animals.
In the hypocupremic group, a "nodular" pattern, with a discrete border
between tumor and brain, was found in 7 of 10 rats (P less than 0.01).
In a second experiment, the brains of 16 tumor-bearing rats were studied by
electron microscopy.
In the 8 normocupremic control rats, cytoplasmic extensions and pseudopodial
protrusions, cytological markers of invasive cells, were prominent at the
tumor-brain interface.
In striking contrast, pseudopodia were absent along the border of the tumors in
the 8 hypocupremic rats.
These findings suggest a biological role of copper in the neoplastic spread of
brain tumor cells.
Pharmacological and metabolic alteration of the cellular microenvironment to
inhibit invasiveness represents a novel therapeutic approach, especially for
tumors of the brain in which malignancy is a function of regional invasiveness.
PMID: 2320207 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2320207&dopt=Abstract
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