Loss of function of Ribonuclease T2, an ancient and phylogenetically conserved RNase, plays a crucial role in ovarian tumorigenesis
In recent years, the role played by the stromal microenvironment has been given growing attention in order to achieve a full understanding of cancer initiation and progression. Because cancer is a tissue-based disease, the integrity of tissue architecture is a major
constraint toward cancer growth. Indeed, a large contribution of the natural resistance to cancer stems from stromal microenvironment
components, the dysregulation of which can facilitate cancer occurrence.
For instance, recent experimental evidence has highlighted the involvement of stromal cells in ovarian carcinogenesis, as epitomized
by ovarian xenografts obtained by a double KO of the murine Dicer and Pten genes. Likewise, we reported the role of an ancient extracellular RNase, called Ribonuclease T2 (RNASET2), within the ovarian stromal microenvironment. Indeed, hyperexpression
of RNASET2 is able to control tumorigenesis by recruiting macrophages (mostly of the anticancer M1 subtype) at the tumor sites.
We present biological data obtained by RNASET2 silencing in the poorly tumorigenetic and highly RNASET2-expressing human
OVCAR3 cell line. RNASET2 knockdown was shown to stimulate in vivo tumor growth early after microinjection of OVCAR3 cells in
nude mice. Moreover, we have investigated by molecular profiling the in vivo expression signature of human and mouse cell xenografts
and disclosed the activation of pathways related to activation of the innate immune response and modulation of ECM components.
Finally, we provide evidence for a role of RNASET2 in triggering an in vitro chemotactic response in macrophages. These results
further highlight the critical role played by the microenvironment in RNASET2-mediated ovarian tumor suppression, which could eventually contribute to better clarify the pathogenesis of this disease.
ACQUATI Francesco;
LUALDI Marta;
BERTILACCIO Sabrina;
MONTI Laura;
TURCONI Giovanna;
FABBRI Marco;
GRIMALDI Annalisa;
ANSELMO Achille;
INFORZATO Antonio;
COLLOTTA Angelo;
CIMETTI Laura;
RIVA Cristina;
GRIBALDO Laura;
GHIA Paolo;
TARAMELLI Roberto;
2013-08-13
NATL ACAD SCIENCES
JRC82090
0027-8424,
www.pnas.org/cgi/doi/10.1073/pnas.1222079110,
https://publications.jrc.ec.europa.eu/repository/handle/JRC82090,
10.1073/pnas.1222079110,
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