Skip to main content
Top
Published in: BMC Cancer 1/2009

Open Access 01-12-2009 | Research article

Freund's vaccine adjuvant promotes Her2/Neu breast cancer

Authors: Michelle S Cotroneo, Jill D Haag, Nicholas R Stapel, Jordy L Waller, Stephan Woditschka, Michael N Gould

Published in: BMC Cancer | Issue 1/2009

Login to get access

Abstract

Background

Inflammation has been linked to the etiology of many organ-specific cancers. Indirect evidence suggests a possible role for inflammation in breast cancer. We investigated whether the systemic inflammation induced by Freund's adjuvant (FA) promotes mammary carcinogenesis in a rat model in which cancer is induced by the neu oncogene.

Methods

The effects of FA on hyperplastic mammary lesions and mammary carcinomas were determined in a neu-induced rat model. The inflammatory response to FA treatment was gauged by measuring acute phase serum haptoglobin. In addition, changes in cell proliferation and apoptosis following FA treatment were assessed.

Results

Rats receiving FA developed twice the number of mammary carcinomas as controls. Systemic inflammation following FA treatment is chronic, as shown by a doubling of the levels of the serum biomarker, haptoglobin, 15 days following initial treatment. We also show that this systemic inflammation is associated with the increased growth of hyperplastic mammary lesions. This increased growth results from a higher rate of cellular proliferation in the absence of changes in apoptosis.

Conclusion

Our data suggests that systemic inflammation induced by Freund's adjuvant (FA) promotes mammary carcinogenesis. It will be important to determine whether adjuvants currently used in human vaccines also promote breast cancer.
Appendix
Available only for authorised users
Literature
1.
go back to reference Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K: Environmental and heritable factors in the causation of cancer – analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 2000, 343: 78-85. 10.1056/NEJM200007133430201.CrossRefPubMed Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K: Environmental and heritable factors in the causation of cancer – analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 2000, 343: 78-85. 10.1056/NEJM200007133430201.CrossRefPubMed
2.
go back to reference Pharoah PD, Antoniou A, Bobrow M, Zimmern RL, Easton DF, Ponder BA: Polygenic susceptibility to breast cancer and implications for prevention. Nat Genet. 2002, 31: 33-36. 10.1038/ng853.CrossRefPubMed Pharoah PD, Antoniou A, Bobrow M, Zimmern RL, Easton DF, Ponder BA: Polygenic susceptibility to breast cancer and implications for prevention. Nat Genet. 2002, 31: 33-36. 10.1038/ng853.CrossRefPubMed
3.
go back to reference Land CE, Tokunaga M, Koyama K, Soda M, Preston DL, Nishimori I, Tokuoka S: Incidence of female breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, 1950–1990. Radiat Res. 2003, 160: 707-717. 10.1667/RR3082.CrossRefPubMed Land CE, Tokunaga M, Koyama K, Soda M, Preston DL, Nishimori I, Tokuoka S: Incidence of female breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, 1950–1990. Radiat Res. 2003, 160: 707-717. 10.1667/RR3082.CrossRefPubMed
4.
go back to reference Yeh IT: Postmenopausal hormone replacement therapy: endometrial and breast effects. Adv Anat Pathol. 2007, 14: 17-24. 10.1097/PAP.0b013e31802ef00f.CrossRefPubMed Yeh IT: Postmenopausal hormone replacement therapy: endometrial and breast effects. Adv Anat Pathol. 2007, 14: 17-24. 10.1097/PAP.0b013e31802ef00f.CrossRefPubMed
5.
go back to reference Balkwill F, Charles KA, Mantovani A: Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell. 2005, 7: 211-217. 10.1016/j.ccr.2005.02.013.CrossRefPubMed Balkwill F, Charles KA, Mantovani A: Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell. 2005, 7: 211-217. 10.1016/j.ccr.2005.02.013.CrossRefPubMed
6.
go back to reference Howe LR, Dannenberg AJ: COX-2 inhibitors for the prevention of breast cancer. J Mammary Gland Biol Neoplasia. 2003, 8: 31-43. 10.1023/A:1025731204719.CrossRefPubMed Howe LR, Dannenberg AJ: COX-2 inhibitors for the prevention of breast cancer. J Mammary Gland Biol Neoplasia. 2003, 8: 31-43. 10.1023/A:1025731204719.CrossRefPubMed
7.
go back to reference Pereg D, Lishner M: Non-steroidal anti-inflammatory drugs for the prevention and treatment of cancer. J Intern Med. 2005, 258: 115-123. 10.1111/j.1365-2796.2005.01519.x.CrossRefPubMed Pereg D, Lishner M: Non-steroidal anti-inflammatory drugs for the prevention and treatment of cancer. J Intern Med. 2005, 258: 115-123. 10.1111/j.1365-2796.2005.01519.x.CrossRefPubMed
8.
go back to reference Giffen PS, Turton J, Andrews CM, Barrett P, Clarke CJ, Fung KW, Munday MR, Roman IF, Smyth R, Walshe K, York MJ: Markers of experimental acute inflammation in the Wistar Han rat with particular reference to haptoglobin and C-reactive protein. Arch Toxicol. 2003, 77: 392-402. 10.1007/s00204-003-0458-7.CrossRefPubMed Giffen PS, Turton J, Andrews CM, Barrett P, Clarke CJ, Fung KW, Munday MR, Roman IF, Smyth R, Walshe K, York MJ: Markers of experimental acute inflammation in the Wistar Han rat with particular reference to haptoglobin and C-reactive protein. Arch Toxicol. 2003, 77: 392-402. 10.1007/s00204-003-0458-7.CrossRefPubMed
9.
go back to reference Wang B, Kennan WS, Yasukawa-Barnes J, Lindstrom MJ, Gould MN: Frequent induction of mammary carcinomas following neu oncogene transfer into in situ mammary epithelial cells of susceptible and resistant rat strains. Cancer Res. 1991, 51: 5649-5654.PubMed Wang B, Kennan WS, Yasukawa-Barnes J, Lindstrom MJ, Gould MN: Frequent induction of mammary carcinomas following neu oncogene transfer into in situ mammary epithelial cells of susceptible and resistant rat strains. Cancer Res. 1991, 51: 5649-5654.PubMed
10.
go back to reference Woditschka S, Haag JD, Sullivan R, Gould MN: A short-term rat mammary carcinogenesis model for the prevention of hormonally responsive and non-responsive in situ carcinomas. Cancer Res Prev. 2009, Woditschka S, Haag JD, Sullivan R, Gould MN: A short-term rat mammary carcinogenesis model for the prevention of hormonally responsive and non-responsive in situ carcinomas. Cancer Res Prev. 2009,
11.
go back to reference Brown NM, Lamartiniere CA: Xenoestrogens alter mammary gland differentiation and cell proliferation in the rat. Environ Health Perspect. 1995, 103: 708-713. 10.2307/3432863.CrossRefPubMedPubMedCentral Brown NM, Lamartiniere CA: Xenoestrogens alter mammary gland differentiation and cell proliferation in the rat. Environ Health Perspect. 1995, 103: 708-713. 10.2307/3432863.CrossRefPubMedPubMedCentral
12.
go back to reference Gould MN: The introduction of activated oncogenes to mammary cells in vivo using retroviral vectors: a new model for the chemoprevention of premalignant and malignant lesions of the breast. J Cell Biochem. 1993, 66-72. 10.1002/jcb.240531113. Suppl 17G Gould MN: The introduction of activated oncogenes to mammary cells in vivo using retroviral vectors: a new model for the chemoprevention of premalignant and malignant lesions of the breast. J Cell Biochem. 1993, 66-72. 10.1002/jcb.240531113. Suppl 17G
13.
go back to reference Woditschka S, Haag JD, Waller JL, Monson DM, Hitt AA, Brose HL, Hu R, Zheng Y, Watson PA, Kim K, Lindstrom MJ, Mau B, Steele VE, Lubet RA, Gould MN: Neu-induced retroviral rat mammary carcinogenesis: a novel chemoprevention model for both hormonally responsive and nonresponsive mammary carcinomas. Cancer Res. 2006, 66: 6884-6891. 10.1158/0008-5472.CAN-05-1823.CrossRefPubMed Woditschka S, Haag JD, Waller JL, Monson DM, Hitt AA, Brose HL, Hu R, Zheng Y, Watson PA, Kim K, Lindstrom MJ, Mau B, Steele VE, Lubet RA, Gould MN: Neu-induced retroviral rat mammary carcinogenesis: a novel chemoprevention model for both hormonally responsive and nonresponsive mammary carcinomas. Cancer Res. 2006, 66: 6884-6891. 10.1158/0008-5472.CAN-05-1823.CrossRefPubMed
14.
go back to reference Jess T, Gamborg M, Matzen P, Munkholm P, Sørensen TI: Increased risk of intestinal cancer in Crohn's disease: a meta-analysis of population-based cohort studies. Am J Gastroenterol. 2005, 100: 2724-2729. 10.1111/j.1572-0241.2005.00287.x.CrossRefPubMed Jess T, Gamborg M, Matzen P, Munkholm P, Sørensen TI: Increased risk of intestinal cancer in Crohn's disease: a meta-analysis of population-based cohort studies. Am J Gastroenterol. 2005, 100: 2724-2729. 10.1111/j.1572-0241.2005.00287.x.CrossRefPubMed
15.
16.
go back to reference De Marzo AM, Platz EA, Sutcliffe S, Xu J, Grönberg H, Drake CG, Nakai Y, Isaacs WB, Nelson WG: Inflammation in prostate carcinogenesis. Nat Rev Cancer. 2007, 7: 256-269. 10.1038/nrc2090.CrossRefPubMedPubMedCentral De Marzo AM, Platz EA, Sutcliffe S, Xu J, Grönberg H, Drake CG, Nakai Y, Isaacs WB, Nelson WG: Inflammation in prostate carcinogenesis. Nat Rev Cancer. 2007, 7: 256-269. 10.1038/nrc2090.CrossRefPubMedPubMedCentral
17.
go back to reference Lindblad EB: Aluminium adjuvants – in retrospect and prospect. Vaccine. 2004, 22: 3658-3668. 10.1016/j.vaccine.2004.03.032.CrossRefPubMed Lindblad EB: Aluminium adjuvants – in retrospect and prospect. Vaccine. 2004, 22: 3658-3668. 10.1016/j.vaccine.2004.03.032.CrossRefPubMed
18.
go back to reference Aguilar JC, Rodriguez EG: Vaccine adjuvants revisited. Vaccine. 2007, 25: 3752-62. 10.1016/j.vaccine.2007.01.111.CrossRefPubMed Aguilar JC, Rodriguez EG: Vaccine adjuvants revisited. Vaccine. 2007, 25: 3752-62. 10.1016/j.vaccine.2007.01.111.CrossRefPubMed
Metadata
Title
Freund's vaccine adjuvant promotes Her2/Neu breast cancer
Authors
Michelle S Cotroneo
Jill D Haag
Nicholas R Stapel
Jordy L Waller
Stephan Woditschka
Michael N Gould
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2009
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-9-19

Other articles of this Issue 1/2009

BMC Cancer 1/2009 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine