Cell cycle–dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity

Romagnani, Paola; Annunziato, Francesco; Lasagni, Laura; Lazzeri, Elena; Beltrame, Chiara; Francalanci, Michela; Uguccioni, Mariagrazia; Galli, Grazia; Cosmi, Lorenzo; Maurenzig, Lucia; Baggiolini, Marco; Maggi, Enrico; Romagnani, Sergio; Serio, Mario

doi:10.1172/jci9775

Cited by 359 publications

(306 citation statements)

References 38 publications

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“…This possibility is raised by the recently reported capacity of human IP -10 for inhibiting endothelial cell growth, although the expression of the IP-10 receptor CXCR3 by normal and transformed endothelial cells is still a matter of controversy. 27,51,52 H5V cell cultures failed to express CXCR3 and were not sensitive to the MVMpmediated production of IP-10 (present work and Ref. [27 ]).…”

Section: Discussionsupporting

confidence: 51%

Suppression of metastatic hemangiosarcoma by a parvovirus MVMp vector transducing the IP-10 chemokine into immunocompetent mice

et al. 2002

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We have previously shown that the growth of human tumor xenografts in immunodeficient mice can be efficiently suppressed upon infection with the autonomous parvovirus H -1 or with cytokine -transducing derivatives thereof. To further evaluate the benefits of implementing parvoviruses in cancer gene therapy, we have created a new recombinant vector, MVMp / IP -10, transducing the immunoactive, antiangiogenic chemokine IP -10, and used this virus to treat syngeneic tumors grown in immunocompetent mice. Intratumoral / intraperitoneal administration of only 3Â10 7 replication units of MVMp / IP -10 per animal strongly inhibited the progression of established H5V cell -induced vascular tumors, a highly malignant mouse model for human cavernous hemangioma and Kaposi's sarcoma. Retardation of recurrent tumor growth and suppression of life -threatening metastatic dissemination to internal organs were accompanied by a striking delay in hemangioma -associated mortality. Parental MVMp did not have a significant effect under these conditions up to the dose of 10 10 infectious units / animal, but had strong antihemangiosarcoma activity when used to infect H5V cells ex vivo prior to implantation. In all cases, virus therapy was very well tolerated. Virus -induced suppression of hemangiosarcoma was dependent on host T cells and associated with intratumoral persistence of IFN -expressing cytotoxic lymphocytes, and led to the reduced expression of hepatic plasminogen activator inhibitor -1 ( PAI -1 ), a metastasis -linked marker. This proof of principle study demonstrates that MVMp / IP -10 can aid the treatment of vascular tumors and that autonomous parvovirus -based vectors can be considered potent tools for cancer gene therapy purposes.

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Section: Discussionsupporting

confidence: 51%

Suppression of metastatic hemangiosarcoma by a parvovirus MVMp vector transducing the IP-10 chemokine into immunocompetent mice

et al. 2002

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“…Candidate molecules for this activity include the chemokines, IP-10 and MIP-1, although it is not completely clear how these molecules function to suppress angiogenesis. It will be interesting to determine whether the shared receptor for these molecules, CXCR3, which is expressed on activated T cells is also expressed on the vascular endothelial cells within the tumours, as has recently been shown for human kidney tumours (Romagnani et al, 2001). An earlier in vitro study has indicated that IL-12-activated CD4 þ and CD8 þ T cells, as well as natural killer (NK) cells can affect the function of endothelial cells (Strasly et al, 2001).…”

Section: Discussionmentioning

confidence: 93%

Mechanism of IL-12 mediated alterations in tumour blood vessel morphology: analysis using whole-tissue mounts

et al. 2003

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New blood vessel formation within tumours is a critical feature for tumour growth. A major limitation in understanding this complex process has been the inability to visualise and analyse vessel formation. Here, we report on the development of a whole-tissue mount technique that allows visualisation of vessel structure. Mice expressing green fluorescent protein (GFP) made it possible to easily see GFP þ vessels within non-GFP-expressing B16 melanoma tumours. The small fragments of tumour used in this technique were also effectively stained with fluorescent probe-conjugated antibodies, allowing characterisation of the vessels based on surface marker phenotype. The vessels within tumour tissue were much more irregular and tortuous compared to those within surrounding normal muscle. B16 tumours stably transfected with the genes for IL-12 were used to assess the effects of this cytokine on tumour growth and vessel formation. The IL-12-expressing tumours grew more slowly and had much smaller blood vessels than the large, webbed vessels characteristic of the parental tumours, effects that were dependent on interferon gamma (IFN-g). Vessels in the parental tumours were found to express VEGFR-3, the receptor for VEGF-C and VEGF-D. Expression of this receptor by the endothelial cells of the blood vessels was lost in the cytokine expressing tumours, thus suggesting a mechanism for the antiangiogenic effects of IL-12. The combination of the whole mount technique and the GFP transgenic mice provides a powerful method for visualising tumour vasculature and characterising the effects of agents such as cytokines.

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“…The CXC chemokines (CXCL9, CXCL10 and CXCL11) inhibit endothelial cell proliferation [67] and suppress tumor angiogenesis in diverse tumors [68][69][70]. Therefore, the balance of angiogenic ELR + vs. angiostatic non-ELR chemokines produced in the tumor microenvironment may determine the development of angiogenesis within a tumor tissue and the consequent clinical outcome.…”

Section: Angiogenesis and Matrix Remodelingmentioning

confidence: 99%

Chemokines in cancer related inflammation

Allavena

Germano

Marchesi

et al. 2011

Experimental Cell Research

200

140

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Chemokines are key players of the cancer-related inflammation. Chemokine ligands and receptors are downstream of genetic events that cause neoplastic transformation and are abundantly expressed in chronic inflammatory conditions which predispose to cancer. Components of the chemokine system affect multiple pathways of tumor progression including: leukocyte recruitment, neo-angiogenesis, tumor cell proliferation and survival, invasion and metastasis.Evidence in pre-clinical and clinical settings suggests that the chemokine system represents a valuable target for the development of innovative therapeutic strategies

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Cell cycle–dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity

Cited by 359 publications

References 38 publications

Suppression of metastatic hemangiosarcoma by a parvovirus MVMp vector transducing the IP-10 chemokine into immunocompetent mice

Suppression of metastatic hemangiosarcoma by a parvovirus MVMp vector transducing the IP-10 chemokine into immunocompetent mice

Mechanism of IL-12 mediated alterations in tumour blood vessel morphology: analysis using whole-tissue mounts

Chemokines in cancer related inflammation

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