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Truncated galectin-3 inhibits tumor growth and metastasis in orthotopic nude mouse model of human breast cancer

John, CM; Leffler, Hakon LU ; Kahl Knutson, Barbro LU ; Svensson, Inga LU and Jarvis, GA (2003) In Clinical Cancer Research 9(6). p.2374-2383
Abstract
Purpose: The goal of this research was to evaluate a potential therapeutic agent for breast cancer based on galectin-3 that has been implicated in tumorigenicity and metastasis of breast cancer. The hypothesis was that therapy with NH2-terminally truncated form of galectin-3 (galectin-3C) will be efficacious for reduction in tumor growth and for inhibition of metastases. Experimental Design: Recombinant human galectin-3 was produced in Escherichia coli from which galectin-3C was derived by collagenase enzyme digestion. Toxicity, pharmacokinetic, and organ biodistribution studies were performed in nude mice. For efficacy studies, nude mice bearing orthotopically implanted tumors derived from breast cancer cell line MDA-MB-435 were treated... (More)
Purpose: The goal of this research was to evaluate a potential therapeutic agent for breast cancer based on galectin-3 that has been implicated in tumorigenicity and metastasis of breast cancer. The hypothesis was that therapy with NH2-terminally truncated form of galectin-3 (galectin-3C) will be efficacious for reduction in tumor growth and for inhibition of metastases. Experimental Design: Recombinant human galectin-3 was produced in Escherichia coli from which galectin-3C was derived by collagenase enzyme digestion. Toxicity, pharmacokinetic, and organ biodistribution studies were performed in nude mice. For efficacy studies, nude mice bearing orthotopically implanted tumors derived from breast cancer cell line MDA-MB-435 were treated with galectin-3C or a vehicle control i.m. twice daily for 90 days. Results: The maximum tolerated dose of galectin-3C in nude mice was determined to be >125 mg/kg without overt adverse effects. The elimination half-life when administered i.m. was found to be 3.0 h in the serum and 4.3 h in the cellular fraction of the blood. Organ biodistribution studies revealed that galectin-3C localized in the liver, kidneys, and spleen but not in the heart or lungs. We found that the mean tumor volumes and weights were statistically significantly less in mice treated with galectin-3C compared with control mice, and that fewer numbers of mice exhibited lymph node metastases in the treated group compared with the control group. Conclusions: Galectin-3C is not overtly toxic, and is efficacious in reducing metastases and tumor volumes and weights in primary tumors in an orthotopic nude mouse model of human breast cancer. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical Cancer Research
volume
9
issue
6
pages
2374 - 2383
publisher
American Association for Cancer Research
external identifiers
  • pmid:12796408
  • wos:000183386000053
  • scopus:0038175029
ISSN
1078-0432
language
English
LU publication?
yes
id
613953c3-a5b4-42a2-8db5-26a41af491d1 (old id 309375)
alternative location
http://clincancerres.aacrjournals.org/cgi/content/abstract/9/6/2374
date added to LUP
2007-09-13 14:25:42
date last changed
2018-02-04 03:34:16
@article{613953c3-a5b4-42a2-8db5-26a41af491d1,
  abstract     = {Purpose: The goal of this research was to evaluate a potential therapeutic agent for breast cancer based on galectin-3 that has been implicated in tumorigenicity and metastasis of breast cancer. The hypothesis was that therapy with NH2-terminally truncated form of galectin-3 (galectin-3C) will be efficacious for reduction in tumor growth and for inhibition of metastases. Experimental Design: Recombinant human galectin-3 was produced in Escherichia coli from which galectin-3C was derived by collagenase enzyme digestion. Toxicity, pharmacokinetic, and organ biodistribution studies were performed in nude mice. For efficacy studies, nude mice bearing orthotopically implanted tumors derived from breast cancer cell line MDA-MB-435 were treated with galectin-3C or a vehicle control i.m. twice daily for 90 days. Results: The maximum tolerated dose of galectin-3C in nude mice was determined to be >125 mg/kg without overt adverse effects. The elimination half-life when administered i.m. was found to be 3.0 h in the serum and 4.3 h in the cellular fraction of the blood. Organ biodistribution studies revealed that galectin-3C localized in the liver, kidneys, and spleen but not in the heart or lungs. We found that the mean tumor volumes and weights were statistically significantly less in mice treated with galectin-3C compared with control mice, and that fewer numbers of mice exhibited lymph node metastases in the treated group compared with the control group. Conclusions: Galectin-3C is not overtly toxic, and is efficacious in reducing metastases and tumor volumes and weights in primary tumors in an orthotopic nude mouse model of human breast cancer.},
  author       = {John, CM and Leffler, Hakon and Kahl Knutson, Barbro and Svensson, Inga and Jarvis, GA},
  issn         = {1078-0432},
  language     = {eng},
  number       = {6},
  pages        = {2374--2383},
  publisher    = {American Association for Cancer Research},
  series       = {Clinical Cancer Research},
  title        = {Truncated galectin-3 inhibits tumor growth and metastasis in orthotopic nude mouse model of human breast cancer},
  volume       = {9},
  year         = {2003},
}