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Journal of Ovarian Research - open access
Background One of side effects of chemotherapy and radiotherapy is the induction of
several factors in various tissues and organs that create a pro-metastatic microenvironment
for cancer cells that survive initial treatment. Methods In the present study, we
employed human ovarian cancer cell line A2780 and immunodeficient mice xenogrfat model
to test effect of both ibuprofen and dexamethasone to ameliorate the therapy-induced
pro-metastatic microenvironment in bone marrow, liver, and lung. Results In our studies,
we found that total body irradiation or administration of cisplatin increases the
metastatic spread of human ovarian cancer cells transplanted into immunodeficient
mice compared with animals unexposed to irradiation or cisplatin. Moreover, conditioned
media harvested from irradiated murine bone marrow, lung, and liver chemoattracted
human ovarian cancer cells, and this chemotactic activity was inactivated by heat,
suggesting a major involvement of peptide or peptide-bound chemoattractants. We also
observed that human ovarian cancer cells proliferate better if exposed to cell debris
harvested from irradiated murine bone marrow. Finally, the pro-metastatic microenvironment
in mice induced by radio- or chemotherapy was significantly ameliorated if animals
were treated at the time of radiochemotherapy administration with non-steroid (ibuprofen)
or steroid (prednisone) anti-inflammatory drugs. Conclusions In summary, we propose
that a radiochemotherapy-induced, pro-metastatic microenvironment plays an important
role in the metastasis of cancer cells that are resistant to treatment. Such cells
have characteristics of cancer stem cells and are highly migratory, and simple, intensive,
anti-inflammatory treatment by non-steroid agents to suppress induction of pro-metastatic
factors after radiochemotherapy would be an interesting anti-metastatic treatment
alternative.
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