Genetic deletion of osteopontin in TRAMP mice skews prostate carcinogenesis from adenocarcinoma to aggressive human-like neuroendocrine cancers

Claudio Tripodo, Elena Jachetti, Giorgio Mauri, Matteo Dugo, Ivano Arioli, Sabina Sangaletti, Barbara Comuzzi, Emma Di Carlo, Silvia Miotti, Mario P. Colombo

Risultato della ricerca: Article

3 Citazioni (Scopus)

Abstract

Osteopontin (OPN) is a secreted glycoprotein, that belongs to the non-structural extracellular matrix (ECM), and its over expression in human prostate cancer has been associated with disease progression, androgen independence and metastatic ability. Nevertheless, the pathophysiology of OPN in prostate tumorigenesis has never been studied. We crossed TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice with OPN deficient (OPN-/-) mice and followed tumor onset and progression in these double mutants. Ultrasound examination detected the early onset of a rapidly growing, homogeneous and spherical tumor in about 60% of OPN-/- TRAMP mice. Such neoplasms seldom occurred in parental TRAMP mice otherwise prone to adenocarcinomas and were characterized for being androgen receptor negative, highly proliferative and endowed with neuroendocrine (NE) features. Gene expression profiling showed up-regulation of genes involved in tumor progression, cell cycle and neuronal differentiation in OPN-deficient versus wild type TRAMP tumors. Downregulated genes included key genes of TGFa pathway, including SMAD3 and Filamin, which were confirmed at the protein level. Furthermore, NE genes and particularly those characterizing early prostatic lesions of OPN-deficient mice were found to correlate with those of human prostate NE tumours. These data underscore a novel role of OPN in the early stages of prostate cancer growth, protecting against the development of aggressive NE tumors.
Lingua originaleEnglish
pagine (da-a)3905-3920
Numero di pagine16
RivistaOncotarget
Volume7
Stato di pubblicazionePublished - 2016

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Osteopontin
Transgenic Mice
Prostate
Carcinogenesis
Adenocarcinoma
Neoplasms
Neuroendocrine Tumors
Genes
Prostatic Neoplasms
Filamins
Androgen Receptors
Gene Expression Profiling
Androgens
Extracellular Matrix
Disease Progression
Glycoproteins
Cell Cycle
Up-Regulation
Down-Regulation
Growth

All Science Journal Classification (ASJC) codes

  • Oncology

Cita questo

Tripodo, C., Jachetti, E., Mauri, G., Dugo, M., Arioli, I., Sangaletti, S., ... Colombo, M. P. (2016). Genetic deletion of osteopontin in TRAMP mice skews prostate carcinogenesis from adenocarcinoma to aggressive human-like neuroendocrine cancers. Oncotarget, 7, 3905-3920.

Genetic deletion of osteopontin in TRAMP mice skews prostate carcinogenesis from adenocarcinoma to aggressive human-like neuroendocrine cancers. / Tripodo, Claudio; Jachetti, Elena; Mauri, Giorgio; Dugo, Matteo; Arioli, Ivano; Sangaletti, Sabina; Comuzzi, Barbara; Di Carlo, Emma; Miotti, Silvia; Colombo, Mario P.

In: Oncotarget, Vol. 7, 2016, pag. 3905-3920.

Risultato della ricerca: Article

Tripodo, C, Jachetti, E, Mauri, G, Dugo, M, Arioli, I, Sangaletti, S, Comuzzi, B, Di Carlo, E, Miotti, S & Colombo, MP 2016, 'Genetic deletion of osteopontin in TRAMP mice skews prostate carcinogenesis from adenocarcinoma to aggressive human-like neuroendocrine cancers', Oncotarget, vol. 7, pagg. 3905-3920.
Tripodo, Claudio ; Jachetti, Elena ; Mauri, Giorgio ; Dugo, Matteo ; Arioli, Ivano ; Sangaletti, Sabina ; Comuzzi, Barbara ; Di Carlo, Emma ; Miotti, Silvia ; Colombo, Mario P. / Genetic deletion of osteopontin in TRAMP mice skews prostate carcinogenesis from adenocarcinoma to aggressive human-like neuroendocrine cancers. In: Oncotarget. 2016 ; Vol. 7. pagg. 3905-3920.
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abstract = "Osteopontin (OPN) is a secreted glycoprotein, that belongs to the non-structural extracellular matrix (ECM), and its over expression in human prostate cancer has been associated with disease progression, androgen independence and metastatic ability. Nevertheless, the pathophysiology of OPN in prostate tumorigenesis has never been studied. We crossed TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice with OPN deficient (OPN-/-) mice and followed tumor onset and progression in these double mutants. Ultrasound examination detected the early onset of a rapidly growing, homogeneous and spherical tumor in about 60{\%} of OPN-/- TRAMP mice. Such neoplasms seldom occurred in parental TRAMP mice otherwise prone to adenocarcinomas and were characterized for being androgen receptor negative, highly proliferative and endowed with neuroendocrine (NE) features. Gene expression profiling showed up-regulation of genes involved in tumor progression, cell cycle and neuronal differentiation in OPN-deficient versus wild type TRAMP tumors. Downregulated genes included key genes of TGFa pathway, including SMAD3 and Filamin, which were confirmed at the protein level. Furthermore, NE genes and particularly those characterizing early prostatic lesions of OPN-deficient mice were found to correlate with those of human prostate NE tumours. These data underscore a novel role of OPN in the early stages of prostate cancer growth, protecting against the development of aggressive NE tumors.",
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AU - Tripodo, Claudio

AU - Jachetti, Elena

AU - Mauri, Giorgio

AU - Dugo, Matteo

AU - Arioli, Ivano

AU - Sangaletti, Sabina

AU - Comuzzi, Barbara

AU - Di Carlo, Emma

AU - Miotti, Silvia

AU - Colombo, Mario P.

PY - 2016

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