A unique mucin immunoenhancing peptide with antitumor properties

Lynn M. Herbert, Joseph F. Grosso, Mantley Dorsey, Tihui Fu, Iafa Keydar, Mabel A. Cejas, Daniel H. Wreschner, Nechama Smorodinski, Diana M Lopez

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Implantation of DA-3 mammary tumor cells into BALB/c mice results in tumor growth, metastatic lesions, and death. These cells were transfected with genes encoding for either the transmembrane (DA-3/TM) or secreted (DA-3/sec) form of human mucin 1 (MUC1). Although the gene for the secreted form lacks the transmembrane and cytoplasmic domains, the 5′ sequences of these mucins are identical; however, the gene for the secreted mucin isoform ends with a sequence encoding for a unique 11 amino acid peptide. The DA-3/TM or DA-3 cells transfected with the neomycin vector only (DA-3/neo) have the same in vivo growth characteristics as the parent cell line. In contrast, DA-3/sec cells fail to grow when implanted in immunocompetent BALB/c animals. DA-3/sec cells implanted in nude mice resulted in tumor development verifying the tumorigenic potential of these cells. Pre-exposure of BALB/c mice to DA-3/sec cells afforded protection against challenge with DA-3/TM or DA-3/neo mammary tumors and the unrelated tumors K7, an osteosarcoma, and RENCA, a renal cell carcinoma. Partial protection against subsequent tumor challenges was also achieved by substituting the 11 amino acid peptide found only in the secreted MUC1 isoform, for the live DA-3/sec cells. Notably, the efficacy of this peptide is not strain restricted because it also retarded the growth of Lewis lung carcinoma cells in C57 BL/6 mice. These findings reveal that a unique peptide present in the secreted MUC1 has immunoenhancing properties and may be a potential agent for use in immunotherapy.

Original languageEnglish
Pages (from-to)8077-8084
Number of pages8
JournalCancer Research
Volume64
Issue number21
DOIs
StatePublished - Nov 1 2004

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Mucins
Peptides
Mucin-1
Protein Isoforms
Growth
Breast Neoplasms
Genes
Lewis Lung Carcinoma
Amino Acids
Neoplasms
Neomycin
Cytoprotection
Osteosarcoma
Renal Cell Carcinoma
Nude Mice
Immunotherapy
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Herbert, L. M., Grosso, J. F., Dorsey, M., Fu, T., Keydar, I., Cejas, M. A., ... Lopez, D. M. (2004). A unique mucin immunoenhancing peptide with antitumor properties. Cancer Research, 64(21), 8077-8084. https://doi.org/10.1158/0008-5472.CAN-04-0853

A unique mucin immunoenhancing peptide with antitumor properties. / Herbert, Lynn M.; Grosso, Joseph F.; Dorsey, Mantley; Fu, Tihui; Keydar, Iafa; Cejas, Mabel A.; Wreschner, Daniel H.; Smorodinski, Nechama; Lopez, Diana M.

In: Cancer Research, Vol. 64, No. 21, 01.11.2004, p. 8077-8084.

Research output: Contribution to journalArticle

Herbert, LM, Grosso, JF, Dorsey, M, Fu, T, Keydar, I, Cejas, MA, Wreschner, DH, Smorodinski, N & Lopez, DM 2004, 'A unique mucin immunoenhancing peptide with antitumor properties', Cancer Research, vol. 64, no. 21, pp. 8077-8084. https://doi.org/10.1158/0008-5472.CAN-04-0853
Herbert LM, Grosso JF, Dorsey M, Fu T, Keydar I, Cejas MA et al. A unique mucin immunoenhancing peptide with antitumor properties. Cancer Research. 2004 Nov 1;64(21):8077-8084. https://doi.org/10.1158/0008-5472.CAN-04-0853
Herbert, Lynn M. ; Grosso, Joseph F. ; Dorsey, Mantley ; Fu, Tihui ; Keydar, Iafa ; Cejas, Mabel A. ; Wreschner, Daniel H. ; Smorodinski, Nechama ; Lopez, Diana M. / A unique mucin immunoenhancing peptide with antitumor properties. In: Cancer Research. 2004 ; Vol. 64, No. 21. pp. 8077-8084.
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