title: Tumor transition zone: a putative new morphological and functional hallmark of tumor aggressiveness.
abstract: A small primary or secondary tumor load can occasionally induce more deleterious effects than a histologically identical larger one. In the four murine models studied herein this enhanced tumor aggressiveness could not be attributed to NRAS mutations or other hereditary changes, differential vascularization of live tumor tissues, or necrosis content. Instead, the main tumor feature associated with a more aggressive behavior was the presence of a high number of vessels, sometimes filled with inflammatory cells, inside a tumor area, which we have identified and designated as the transition zone between the live and the necrotic zones. Our experiments suggest that during tumor growth, different cachectic factors are produced within the transition and necrotic zones by dying tumor cells and by tumor infiltrating macrophages only reaching the general circulation through the vessels present in the transition zone. Therefore, a small tumor displaying high vascularization of its transition area could be harmful to its host, while, in contrast, a large tumor could behave as a relatively benign one if its transition zone exhibited little or no vascularization, and in consequence its cachectic factors remained "trapped." Similar histological images to those observed in mice were seen in a significant percentage of human cancer biopsies, raising the possibility that such images might have a prognostic value.
authors.affiliation: División Medicina Experimental, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Pacheco de Melo 3081, 1425 Buenos Aires, Argentina.
authors.forename: Oscar D
authors.initials: OD
authors.lastname: Bustuoabad
authors.forename: Raúl A
authors.initials: RA
authors.lastname: Ruggiero
authors.forename: Pedro
authors.initials: P
authors.lastname: di Gianni
authors.forename: M Gabriela
authors.initials: MG
authors.lastname: Lombardi
authors.forename: Carolina
authors.initials: C
authors.lastname: Belli
authors.forename: Gabriela V
authors.initials: GV
authors.lastname: Camerano
authors.forename: Graciela
authors.initials: G
authors.lastname: Dran
authors.forename: Carolina
authors.initials: C
authors.lastname: Schere-Levy
authors.forename: Héctor
authors.initials: H
authors.lastname: Costa
authors.forename: Martin A
authors.initials: MA
authors.lastname: Isturiz
authors.forename: Marina
authors.initials: M
authors.lastname: Narvaitz
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Victoria de los A
authors.initials: Vde L
authors.lastname: Bustuoabad
authors.forename: Roberto P
authors.initials: RP
authors.lastname: Meiss
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009336:Necrosis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm