Gene Set: MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP

Standard name MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP
Systematic name M11891
Brief description The postradiation tumor escape signature: genes up-regulated in tumors from irradiated stroma vs those from non-irradiated stroma.
Full description or abstract Radiotherapy is widely used to treat human cancer. Patients locally recurring after radiotherapy, however, have increased risk of metastatic progression and poor prognosis. The clinical management of postradiation recurrences remains an unresolved issue. Tumors growing in preirradiated tissues have an increased fraction of hypoxic cells and are more metastatic, a condition known as tumor bed effect. The transcription factor hypoxia inducible factor (HIF)-1 promotes invasion and metastasis of hypoxic tumors, but its role in the tumor bed effect has not been reported. Here, we show that tumor cells derived from SCCVII and HCT116 tumors growing in a preirradiated bed, or selected in vitro through repeated cycles of severe hypoxia, retain invasive and metastatic capacities when returned to normoxia. HIF activity, although facilitating metastatic spreading of tumors growing in a preirradiated bed, is not essential. Through gene expression profiling and gain- and loss-of-function experiments, we identified the matricellular protein CYR61 and alphaVbeta5 integrin as proteins cooperating to mediate these effects. The anti-alphaV integrin monoclonal antibody 17E6 and the small molecular alphaVbeta3/alphaVbeta5 integrin inhibitor EMD121974 suppressed invasion and metastasis induced by CYR61 and attenuated metastasis of tumors growing within a preirradiated field. These results represent a conceptual advance to the understanding of the tumor bed effect and identify CYR61 and alphaVbeta5 integrin as proteins that cooperate to mediate metastasis. They also identify alphaV integrin inhibition as a potential therapeutic approach for preventing metastasis in patients at risk for postradiation recurrences.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18794119   Authors: Monnier Y,Farmer P,Bieler G,Imaizumi N,Sengstag T,Alghisi GC,Stehle JC,Ciarloni L,Andrejevic-Blant S,Moeckli R,Mirimanoff RO,Goodman SL,Delorenzi M,Regg C
Exact source Table 1S: fc(NIR-IR) > 0
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Organism Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
Source platform AFFY_Mouse430
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Version history 3.0: First introduced

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