Multiple roles of perforin in hampering ERBB-2 (Her-2/neu) carcinogenesis in transgenic male mice

Macagno, Marco, Bandini, Silvio, Stramucci, Lorenzo, Quaglino, Elena, Conti, Laura, Balmas, Elisa, Smyth, Mark J., Lollini, Pier-Luigi, Musiani, Piero, Forni, Guido, Iezzi, Manuela and Cavallo, Federica (2014) Multiple roles of perforin in hampering ERBB-2 (Her-2/neu) carcinogenesis in transgenic male mice. Journal of Immunology, 192 11: 5434-5441. doi:10.4049/jimmunol.1301248

Author Macagno, Marco
Bandini, Silvio
Stramucci, Lorenzo
Quaglino, Elena
Conti, Laura
Balmas, Elisa
Smyth, Mark J.
Lollini, Pier-Luigi
Musiani, Piero
Forni, Guido
Iezzi, Manuela
Cavallo, Federica
Title Multiple roles of perforin in hampering ERBB-2 (Her-2/neu) carcinogenesis in transgenic male mice
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 1550-6606
Publication date 2014-06-01
Year available 2014
Sub-type Article (original research)
DOI 10.4049/jimmunol.1301248
Open Access Status DOI
Volume 192
Issue 11
Start page 5434
End page 5441
Total pages 8
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Collection year 2015
Language eng
Formatted abstract
Perforin (pfp)-mediated cytotoxicity is one of the principal immunosurveillance mechanisms involved in the fight against cancer. However, its importance in spontaneous epithelial cancer is still poorly defined. In this study, we use a realistic mouse model that displays many features that are equivalent to human pathology to evaluate the role of pfp-dependent immunosurveillance by comparing tumor progression in rat ERBB-2 (neu) transgenic, pfp-proficient (neu+/pfp+) or pfp-deficient (neu+/pfp) BALB/c male mice. Adult neu+/pfp+ males developed poorly differentiated salivary carcinomas, whereas neu+/pfp males displayed their salivary carcinomas noticeably earlier and showed zones of more highly differentiated tumor, indicating that pfp-mediated immunosurveillance is able not only to delay the growth kinetic of an aggressive epithelial tumor, but also to shape its histology. The role of pfp-mediated immunosurveillance appeared to be of even more dramatic importance against the less aggressive male mammary carcinomas. In neu+/pfp+ males, the incidence of mammary carcinomas was a sporadic and late event. In contrast, in neu+/pfp males their incidence was four-fold higher. This higher cancer incidence was associated with a 2-fold higher occurrence of persisting mammary remnants, a major risk factor for mammary cancer in male mice, and one that would appear to be due to pfp’s previously unidentified involvement in male mammary gland rejection during embryogenesis. This work thus provides further proof of the complex role that the immune system plays in the body and gives new insight into the pathogenesis of epithelial tumors, demonstrating that the penetrance and malignancy of a tumor may be dramatically affected by pfp-dependent mechanisms.
Keyword Perforin
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
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