title: AngioMatrix, a signature of the tumor angiogenic switch-specific matrisome, correlates with poor prognosis for glioma and colorectal cancer patients.
abstract: Angiogenesis represents a rate-limiting step during tumor progression. Targeting angiogenesis is already applied in cancer treatment, yet limits of anti-angiogenic therapies have emerged, notably because tumors adapt and recur after treatment. Therefore, there is a strong need to better understand the molecular and cellular mechanisms underlying tumor angiogenesis. Using the RIP1-Tag2 transgenic murine model, we identified 298 genes that are deregulated during the angiogenic switch, revealing an ingression/expansion of specific stromal cell types including endothelial cells and pericytes, but also macrophages and perivascular mesenchymal cells. Canonical TGF-β signaling is up-regulated during the angiogenic switch, especially in tumor-associated macrophages and fibroblasts. The matrisome, comprising extracellular matrix (ECM) and ECM-associated molecules, is significantly enriched, which allowed us to define the AngioMatrix signature as the 110 matrisomal genes induced during the RIP1-Tag2 angiogenic switch. Several AngioMatrix molecules were validated at expression level. Ablation of tenascin-C, one of the most highly induced ECM molecules during the switch, resulted in reduced angiogenesis confirming its important role. In human glioma and colorectal samples, the AngioMatrix signature correlates with the expression of endothelial cell markers, is increased with tumor progression and finally correlates with poor prognosis demonstrating its diagnostic and therapeutic potential.
authors.affiliation: Inserm U1109, MN3T team, Molière, Strasbourg, 67200, France. Université de Strasbourg, Strasbourg, 67000, France. LabEx Medalis, Université de Strasbourg, Strasbourg, 67000, France. Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, 67000, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Langlois
authors.affiliation: Inserm U1109, MN3T team, Molière, Strasbourg, 67200, France. Université de Strasbourg, Strasbourg, 67000, France. LabEx Medalis, Université de Strasbourg, Strasbourg, 67000, France. Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, 67000, France.
authors.forename: Falk
authors.initials: F
authors.lastname: Saupe
authors.affiliation: Inserm U1109, MN3T team, Molière, Strasbourg, 67200, France. Université de Strasbourg, Strasbourg, 67000, France. LabEx Medalis, Université de Strasbourg, Strasbourg, 67000, France. Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, 67000, France.
authors.forename: Tristan
authors.initials: T
authors.lastname: Rupp
authors.affiliation: Inserm U1109, MN3T team, Molière, Strasbourg, 67200, France. Université de Strasbourg, Strasbourg, 67000, France. LabEx Medalis, Université de Strasbourg, Strasbourg, 67000, France. Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, 67000, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Arnold
authors.affiliation: Inserm U1109, MN3T team, Molière, Strasbourg, 67200, France. Université de Strasbourg, Strasbourg, 67000, France. LabEx Medalis, Université de Strasbourg, Strasbourg, 67000, France. Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, 67000, France.
authors.forename: Michaël
authors.initials: M
authors.lastname: van der Heyden
authors.affiliation: Inserm U1109, MN3T team, Molière, Strasbourg, 67200, France. Université de Strasbourg, Strasbourg, 67000, France. LabEx Medalis, Université de Strasbourg, Strasbourg, 67000, France. Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, 67000, France.
authors.forename: Gertraud
authors.initials: G
authors.lastname: Orend
authors.affiliation: Inserm U1109, MN3T team, Molière, Strasbourg, 67200, France. Université de Strasbourg, Strasbourg, 67000, France. LabEx Medalis, Université de Strasbourg, Strasbourg, 67000, France. Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, 67000, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hussenet
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000401:mortality; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000502:physiology*; D020869:Gene Expression Profiling; D005910:Glioma / Q000098:blood supply / Q000235:genetics* / Q000401:mortality; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D020690:GTPase-Activating Proteins; C490620:Ralbp1 protein, mouse