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Concordant morphologic and gene expression data show that a vaccine halts HER-2/neu preneoplastic lesions
Elena Quaglino, … , Raffaele Calogero, Federica Cavallo
Elena Quaglino, … , Raffaele Calogero, Federica Cavallo
Published March 1, 2004
Citation Information: J Clin Invest. 2004;113(5):709-717. https://doi.org/10.1172/JCI19850.
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Article Immunology

Concordant morphologic and gene expression data show that a vaccine halts HER-2/neu preneoplastic lesions

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Abstract

While much experimental data shows that vaccination efficiently inhibits a subsequent challenge by a transplantable tumor, its ability to inhibit the progress of autochthonous preneoplastic lesions is virtually unknown. In this article, we show that a combined DNA and cell vaccine persistently inhibits such lesions in a murine HER-2/neu mammary carcinogenesis model. At 10 weeks of age, all of the ten mammary gland samples from HER-2/neu–transgenic mice displayed foci of hyperplasia that progressed to invasive tumors. Vaccination with plasmids coding for the transmembrane and extracellular domain of rat p185neu followed by a boost with rp185neu+ allogeneic cells secreting IFN-γ kept 48% of mice tumor free. At 22 weeks, their mammary glands were indistinguishable from those of 10-week-old untreated mice. Furthermore, the transcription patterns of the two sets of glands coincided. Of the 12,000 genes analyzed, 17 were differentially expressed and related to the antibody response. The use of B cell knockout mice as well as the concordance of morphologic and gene expression data demonstrated that the Ab response is the main mechanism facilitating tumor growth arrest. This finding suggests that a new way can be found to secure the immunologic control of the progression of HER-2/neu preneoplastic lesions.

Authors

Elena Quaglino, Simona Rolla, Manuela Iezzi, Michela Spadaro, Piero Musiani, Carla De Giovanni, Pier Luigi Lollini, Stefania Lanzardo, Guido Forni, Remo Sanges, Stefania Crispi, Pasquale De Luca, Raffaele Calogero, Federica Cavallo

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Figure 5

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PCA analysis and 2D hierarchical clustering of virtual two-dye experimen...
PCA analysis and 2D hierarchical clustering of virtual two-dye experiments. (A) PCA projection showing that the overall analyzed data set is organized in two large clusters on the first two principal components. The two clusters discriminate genes on the expression differences existing between wk22nt mice and the other two groups. In both clusters, wk10nt and wk22pb are grouped together and they are separated from wk22nt. (B) PCA projection showing that the third principal component does not contribute at all to the data clustering. (C) Profiles of PCA cluster 1: 1,122 probe sets upmodulated in wk22pb/wk10nt with respect to wk22nt; clusters a–e represent the probe sets upmodulated only in wk22pb. (D) Profiles of PCA cluster 2: 1,057 probe sets downmodulated in wk22pb/wk10nt with respect to wk22nt.

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