Publication: Tumor DNA circulating in the plasma might play a role in metastasis. The hypothesis of the genometastasis
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Date
1999
Authors
García-Olmo, Dolores C. ; Ontañon, J. ; Martinez, E.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Background: Clinical and experimental
observations suggest that more than one pathway might
be involved in the development of metastases. In the
present study, we examined the presence of tumor DNA
in plasma using an experimental model in which tumor
cells were modified with a genome-associated tag. We
also investigated whether plasma of tumor-bearing rats
had any effect on cultured cells and healthy animals.
Methods: Transfected cancer cells (DHDlK12-PROb
stably transfected with pCDNA3.1CAT.) were injected
subcutaneously into the chest of BD-IX rats. Animals
were divided into ten groups according to the time
between injection of tumor cells and euthanasia. Prior to
euthanasia (2-14 week), blood samples were collected by
cardiac puncture. To detect circulating tumor cells and
CAT-encoding DNA in plasma, we performed PCR with
nested primers. Fifty samples of plasma were chosen at
random to supplement the medium of fifty cultures of
DHD cells for 10-12 days. PCR for the detection of CAT
DNA in cells was performed approximately one to two
months later. Four healthy rats received an
intraperitoneal injection of plasma from a tumor-bearing
rat five times at week for 4 to 6 weeks. Animals were
sacrificed and samples of liver, kidney, spleen,
omentum, blood and lung were processed by PCR for
the detection of CAT DNA. Results: Detection of CAT
DNA in plasma was slightly more frequent than in the
buffy-coat fraction. All surviving cultures that had been
supplemented with plasma were positive at some point
for CAT DNA. In all four healthy animals injected with
plasma of tumor-bearing rats, the marker gene for CAT
was found in extracts of lungs. Conclusion: Our present
observation lead us to propose the following hypothesis.
Metastases might develop as a result of transfection of
susceptible cells in distant target organs with dominant
oncogenes that are present in the circulating plasma and
are derived from the primary tumor.
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