Abstract
We have recently shown that administration of α-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), the first and rate-limiting enzyme in polyamine (PA) biosynthesis reduces pulmonary metastasis from MDA-MB-435 breast cancer xenografts in nude mice. The present experiments were designed to further explore PA involvement in breast cancer metastasis, using GFP-tagged MDA-MB-435 cells that can be tracked at the single cell level. Administration of DFMO significantly reduced the number of mice with pulmonary metastasis as well as the number of metastases per mouse. Both single-cell and multicellular metastatic deposits were similarly suppressed, thus suggesting that DFMO was inhibiting lung colonization by tumor cells rather than preventing progression of single-cell deposits to overt metastasis. DFMO administration also significantly reduced local recurrences following removal of the primary tumor. Prolongation of DFMO treatment to 14 weeks did not yield a superior antimetastatic effect beyond that provided by a 10-week course of therapy. Discontinuation of DFMO, on the other hand, was associated with local regrowth of the tumors and, possibly, recurrence of pulmonary metastasis. These data provide a rationale for testing the efficacy of anti-PA treatment within the context of adjuvant therapy of breast cancer.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 321-325 |
| Number of pages | 5 |
| Journal | Clinical and Experimental Metastasis |
| Volume | 20 |
| Issue number | 4 |
| DOIs | |
| State | Published - Jul 2 2003 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
Cite this
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Effects of α-difluoromethylornithine on local recurrence and pulmonary metastasis from MDA-MB-435 breast cancer xenografts in nude mice. / Manni, Andrea; Washington, Sharlene; Craig, Laura; Cloud, Michael; Griffith, James W.; Verderame, Michael; Texter, Lindsay J.; Mauger, David; Demers, Laurence; Harms, John F.; Welch, Danny R.
In: Clinical and Experimental Metastasis, Vol. 20, No. 4, 02.07.2003, p. 321-325.Research output: Contribution to journal › Article
TY - JOUR
T1 - Effects of α-difluoromethylornithine on local recurrence and pulmonary metastasis from MDA-MB-435 breast cancer xenografts in nude mice
AU - Manni, Andrea
AU - Washington, Sharlene
AU - Craig, Laura
AU - Cloud, Michael
AU - Griffith, James W.
AU - Verderame, Michael
AU - Texter, Lindsay J.
AU - Mauger, David
AU - Demers, Laurence
AU - Harms, John F.
AU - Welch, Danny R.
PY - 2003/7/2
Y1 - 2003/7/2
N2 - We have recently shown that administration of α-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), the first and rate-limiting enzyme in polyamine (PA) biosynthesis reduces pulmonary metastasis from MDA-MB-435 breast cancer xenografts in nude mice. The present experiments were designed to further explore PA involvement in breast cancer metastasis, using GFP-tagged MDA-MB-435 cells that can be tracked at the single cell level. Administration of DFMO significantly reduced the number of mice with pulmonary metastasis as well as the number of metastases per mouse. Both single-cell and multicellular metastatic deposits were similarly suppressed, thus suggesting that DFMO was inhibiting lung colonization by tumor cells rather than preventing progression of single-cell deposits to overt metastasis. DFMO administration also significantly reduced local recurrences following removal of the primary tumor. Prolongation of DFMO treatment to 14 weeks did not yield a superior antimetastatic effect beyond that provided by a 10-week course of therapy. Discontinuation of DFMO, on the other hand, was associated with local regrowth of the tumors and, possibly, recurrence of pulmonary metastasis. These data provide a rationale for testing the efficacy of anti-PA treatment within the context of adjuvant therapy of breast cancer.
AB - We have recently shown that administration of α-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), the first and rate-limiting enzyme in polyamine (PA) biosynthesis reduces pulmonary metastasis from MDA-MB-435 breast cancer xenografts in nude mice. The present experiments were designed to further explore PA involvement in breast cancer metastasis, using GFP-tagged MDA-MB-435 cells that can be tracked at the single cell level. Administration of DFMO significantly reduced the number of mice with pulmonary metastasis as well as the number of metastases per mouse. Both single-cell and multicellular metastatic deposits were similarly suppressed, thus suggesting that DFMO was inhibiting lung colonization by tumor cells rather than preventing progression of single-cell deposits to overt metastasis. DFMO administration also significantly reduced local recurrences following removal of the primary tumor. Prolongation of DFMO treatment to 14 weeks did not yield a superior antimetastatic effect beyond that provided by a 10-week course of therapy. Discontinuation of DFMO, on the other hand, was associated with local regrowth of the tumors and, possibly, recurrence of pulmonary metastasis. These data provide a rationale for testing the efficacy of anti-PA treatment within the context of adjuvant therapy of breast cancer.
UR - http://www.scopus.com/inward/record.url?scp=0038199842&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038199842&partnerID=8YFLogxK
U2 - 10.1023/A:1024055522067
DO - 10.1023/A:1024055522067
M3 - Article
C2 - 12856719
AN - SCOPUS:0038199842
VL - 20
SP - 321
EP - 325
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
SN - 0262-0898
IS - 4
ER -