title: Imaging of Angiotropism/Vascular Co-Option in a Murine Model of Brain Melanoma: Implications for Melanoma Progression along Extravascular Pathways.
abstract: Angiotropism/pericytic mimicry and vascular co-option involve tumor cell interactions with the abluminal vascular surface. These two phenomena may be closely related. However, investigations of the two processes have developed in an independent fashion and different explanations offered as to their biological nature. Angiotropism describes the propensity of tumor cells to spread distantly via continuous migration along abluminal vascular surfaces, or extravascular migratory metastasis (EVMM). Vascular co-option has been proposed as an alternative mechanism by which tumors cells may gain access to a blood supply. We have used a murine brain melanoma model to analyze the interactions of GFP human melanoma cells injected into the mouse brain with red fluorescent lectin-labeled microvascular channels. Results have shown a striking spread of melanoma cells along preexisting microvascular channels and features of both vascular co-option and angiotropism/pericytic mimicry. This study has also documented the perivascular expression of Serpin B2 by angiotropic melanoma cells in the murine brain and in human melanoma brain metastases. Our findings suggest that vascular co-option and angiotropism/pericytic mimicry are closely related if not identical processes. Further studies are needed in order to establish whether EVMM is an alternative form of cancer metastasis in addition to intravascular cancer dissemination.
authors.affiliation: California NanoSystems Institute, Los Angeles, CA, 90095 USA.|Department of Chemistry and Biochemistry University of California, Los Angeles, CA, 90095 USA.
authors.forename: Laurent A
authors.initials: LA
authors.lastname: Bentolila
authors.affiliation: Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095 USA.
authors.forename: Roshini
authors.initials: R
authors.lastname: Prakash
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, 8091 Zurich, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Mihic-Probst
authors.affiliation: Department of Pathology and Laboratory Medicine and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California Los Angeles UCLA, Los Angeles, CA, USA.
authors.forename: Madhuri
authors.initials: M
authors.lastname: Wadehra
authors.affiliation: National Institutes of Health, Bethesda, MD, USA.
authors.forename: Hynda K
authors.initials: HK
authors.lastname: Kleinman
authors.affiliation: Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095 USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Carmichael
authors.affiliation: Orthopedic Hospital Research Center and Broad Stem Cell Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.|MRC Center for Regenerative Medicine and BHF Center for Cardiovascular Science, Queens Medical Research Institute University of Edinburgh, Edinburgh, UK.
authors.forename: Bruno
authors.initials: B
authors.lastname: Péault
authors.affiliation: Department of Pathology, Institut Curie, and University of Paris Réne Descartes, Paris, France.
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Barnhill
authors.affiliation: Department of Translational Research, Institut Curie, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Lugassy
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply / Q000503:physiopathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000737:chemistry; D008164:Luminescent Proteins / Q000378:metabolism; D008545:Melanoma / Q000098:blood supply / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D020286:Pericytes / Q000378:metabolism; D017396:Plasminogen Activator Inhibitor 2 / Q000378:metabolism; D012878:Skin Neoplasms / Q000098:blood supply / Q000503:physiopathology*; D000097573:Red Fluorescent Protein
chemical_list: D049452:Green Fluorescent Proteins; D037102:Lectins; D008164:Luminescent Proteins; D017396:Plasminogen Activator Inhibitor 2; D000097573:Red Fluorescent Protein