title: Hypoxia increases breast cancer cell-induced lymphatic endothelial cell migration.
abstract: Because tumors are characterized by hypoxic environments, we used a novel in vitro noninvasive magnetic resonance imaging assay to examine the influence of invasive MDA-MB-231 breast cancer cells on the invasion and migration of human dermal lymphatic microvascular endothelial cells (HMVEC-dLy) under normoxic and hypoxic conditions. Nonmalignant immortalized MCF-12A human mammary epithelial cells instead of cancer cells or chambers with HMVEC-dLy alone were used as controls for comparison. HMVEC-dLy cells were labeled with a T(2) contrast agent (Feridex), and their invasion and migration through extracellular matrix under normoxic and hypoxic conditions were monitored using magnetic resonance imaging. A significant increase in the invasion and migration of HMVEC-dLy cells was detected in the presence of cancer cells, which further increased significantly under hypoxic conditions. HMVEC-dLy cells formed interconnecting strands extending toward the cancer cells under normoxic but not under hypoxic conditions. Following reoxygenation, these interconnecting strands, extending from HMVEC-dLy cells toward the cancer cells, were observed. These data demonstrate the importance of hypoxia in lymphatic endothelial cell invasion and migration through extracellular matrix in the presence of cancer cells.
authors.affiliation: JHU ICMIC Program, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Mikhaylova
authors.forename: Noriko
authors.initials: N
authors.lastname: Mori
authors.forename: Flonné B
authors.initials: FB
authors.lastname: Wildes
authors.forename: Piotr
authors.initials: P
authors.lastname: Walczak
authors.forename: Barjor
authors.initials: B
authors.lastname: Gimi
authors.forename: Zaver M
authors.initials: ZM
authors.lastname: Bhujwalla
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002450:Cell Communication; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen; D004338:Drug Combinations; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D000860:Hypoxia / Q000150:complications*; D007797:Laminin; D008279:Magnetic Resonance Imaging; D053758:Nanoparticles; D009361:Neoplasm Invasiveness; D010100:Oxygen / Q000378:metabolism; D011509:Proteoglycans; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D042582:Vascular Endothelial Growth Factor C
chemical_list: D004338:Drug Combinations; D005290:Ferric Compounds; D007797:Laminin; D011509:Proteoglycans; D042582:Vascular Endothelial Growth Factor C; C059485:matrigel; C000499:ferric oxide; D003094:Collagen; D010100:Oxygen