Effects of α-difluoromethylornithine on local recurrence and pulmonary metastasis from MDA-MB-435 breast cancer xenografts in nude mice

Andrea Manni, Sharlene Washington, Laura Craig, Michael Cloud, James W. Griffith, Michael Verderame, Lindsay J. Texter, David Mauger, Laurence Demers, John F. Harms, Danny R. Welch

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)321-325
Number of pages5
JournalClinical and Experimental Metastasis
Volume20
Issue number4
DOIs
StatePublished - Jul 2 2003

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Eflornithine
Heterografts
Nude Mice
Breast Neoplasms
Neoplasm Metastasis
Recurrence
Lung
Polyamines
Neoplasms
Enzymes
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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. / Effects of α-difluoromethylornithine on local recurrence and pulmonary metastasis from MDA-MB-435 breast cancer xenografts in nude mice. In: Clinical and Experimental Metastasis. 2003 ; Vol. 20, No. 4. pp. 321-325.
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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 journalArticle

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AU - Manni, Andrea

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