The antitumor potential of Interleukin-27 in prostate cancer
Metrics: PDF 3542 views | HTML 4170 views | ?
Emma Di Carlo1,2, Carlo Sorrentino1,2, Alessia Zorzoli3, Serena Di Meo1,2, Maria Grazia Tupone1,2, Emanuela Ognio4, Gabriella Mincione2,5 and Irma Airoldi3
1 Department of Medicine and Sciences of Aging, Section of Anatomic Pathology and Molecular Medicine, “G. d’Annunzio” University, Chieti, Italy
2 Ce.S.I. Aging Research Center, “G. d’Annunzio” University Foundation, Chieti, Italy
3 Laboratory of Oncology, Istituto Giannina Gaslini, Genova, Italy
4 Animal Facility, IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
5 Department of Experimental and Clinical Sciences, “G. d’Annunzio” University, Chieti, Italy
Emma Di Carlo, email:
Keywords: prostate cancer, interleukin-27, cytokines, immunotherapy, anti-tumor activity, tumor microenvironment
Received: September 19, 2013 Accepted: December 28, 2013 Published: December 28, 2013
Prostate cancer (PCa) is of increasing significance worldwide as a consequence of the population ageing. Fragile elderly patients may particularly benefit from noninvasive and well tolerable immunotherapeutic approaches. Preclinical studies have revealed that the immune-regulatory cytokine IL-27 may exert anti-tumor activities in a variety of tumor types without discernable toxicity. We, thus, investigated whether IL-27 may function as anti-tumor agent in human (h) PCa and analyzed the rationale for its clinical application.
In vitro, IL-27 treatment significantly inhibited proliferation and reduced the angiogenic potential of hPCa cells by down-regulating the pro-angiogenesis-related genes fms-related tyrosine kinase (FLT)1, prostaglandin G/H synthase 1/cyclooxygenase-1 (PTGS1/COX-1) and fibroblast growth factor receptor (FGFR)3. In addition, IL-27 up-regulated the anti-angiogenesis-related genes such as CXCL10 and TIMP metallopeptidase inhibitor 3 (TIMP3). In vivo, IL-27 reduced proliferation and vascularization in association with ischemic necrosis of tumors developed after PC3 or DU145 cell injection in athymic nude mice. In patients’ prostate tissues, IL-27R was expressed by normal epithelia and low grade PCa and lost by high tumor grade and stages. Nevertheless, IL-27R was expressed by CD11c+, CD4+ and CD8+ leukocytes infiltrating the tumor and draining lymph nodes.
These data lead to the conclusion that i) IL-27’s anti-PCa potential may be fully exploited in patients with well-differentiated, localized IL-27R positive PCa, since in this case it may act on both cancerous epithelia and the tumor microenvironment; ii) PCa patients bearing high grade and stage tumor that lack IL-27R may benefit, however, from IL-27’s immune-stimulatory properties.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.