title: Heterogeneous perivascular cell coverage affects breast cancer metastasis and response to chemotherapy.
abstract: Angiogenesis and co-optive vascular remodeling are prerequisites of solid tumor growth. Vascular heterogeneity, notably perivascular composition, may play a critical role in determining the rate of cancer progression. The contribution of vascular pericyte heterogeneity to cancer progression and therapy response is unknown. Here, we show that angiopoietin-2 (Ang2) orchestrates pericyte heterogeneity in breast cancer with an effect on metastatic disease and response to chemotherapy. Using multispectral imaging of human breast tumor specimens, we report that perivascular composition, as defined by the ratio of PDGFRβ-and desmin+pericytes, provides information about the response to epirubicin but not paclitaxel. Using 17 distinct patient-derived breast cancer xenografts, we demonstrate a cancer cell-derived influence on stromal Ang2 production and a cancer cell-defined control over tumor vasculature and perivascular heterogeneity. The aggressive features of tumors and their distinct response to therapies may thus emerge by the cancer cell-defined engagement of distinct and heterogeneous angiogenic programs.
authors.affiliation: Department of Cancer Biology.
authors.forename: Jiha
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Cancer Biology.
authors.forename: Pedro Correa
authors.initials: PC
authors.lastname: de Sampaio
authors.affiliation: Department of Cancer Biology.
authors.forename: Donna Marie
authors.initials: DM
authors.lastname: Lundy
authors.affiliation: Department of Cancer Biology.
authors.forename: Qian
authors.initials: Q
authors.lastname: Peng
authors.affiliation: Department of Investigational Cancer Therapeutics, and.
authors.forename: Kurt W
authors.initials: KW
authors.lastname: Evans
authors.affiliation: Department of Cancer Biology.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Sugimoto
authors.affiliation: Department of Veterinary Medicine and Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Mihai
authors.initials: M
authors.lastname: Gagea
authors.affiliation: Discovery Oncology, Roche Pharmaceutical Research and Early Development, (pRED), Roche Innovation Center, Munich, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Kienast
authors.affiliation: Department of Anatomic Pathology, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Nayra Soares do
authors.initials: NSD
authors.lastname: Amaral
authors.affiliation: Molecular Gynecology Laboratory, Gynecology Department, Federal University of São Paulo, Brazil.
authors.forename: Rafael Malagoli
authors.initials: RM
authors.lastname: Rocha
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Oncology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Hans Petter
authors.initials: HP
authors.lastname: Eikesdal
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Oncology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Per Eystein
authors.initials: PE
authors.lastname: Lønning
authors.affiliation: Department of Investigational Cancer Therapeutics, and.|Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Funda
authors.initials: F
authors.lastname: Meric-Bernstam
authors.affiliation: Department of Cancer Biology.
authors.forename: Valerie S
authors.initials: VS
authors.lastname: LeBleu