Co-Expression of α9β1 Integrin and VEGF-D Confers Lymphatic Metastatic Ability to a Human Breast Cancer Cell Line MDA-MB-468LN

INTRODUCTION AND OBJECTIVES: Lymphatic metastasis is a common occurrence in human breast cancer, mechanisms remaining poorly understood. MDA-MB-468LN (468LN), a variant of the MDA-MB-468GFP (468GFP) human breast cancer cell line, produces extensive lymphatic metastasis in nude mice. 468LN cells differentially express α9β1 integrin, a receptor for lymphangiogenic factors VEGF-C/-D. We explored whether (1) differential production of VEGF-C/-D by 468LN cells provides an autocrine stimulus for cellular motility by interacting with α9β1 and a paracrine stimulus for lymphangiogenesis in vitro as measured with capillary-like tube formation by human lymphatic endothelial cells (HMVEC-dLy); (2) differential expression of α9 also promotes cellular motility/invasiveness by interacting with macrophage derived factors; (3) stable knock-down of VEGF-D or α9 in 468LN cells abrogates lymphangiogenesis and lymphatic metastasis in vivo in nude mice. RESULTS: A comparison of expression of cyclo-oxygenase (COX)-2 (a VEGF-C/-D inducer), VEGF-C/-D and their receptors revealed little COX-2 expression by either cells. However, 468LN cells showed differential VEGF-D and α9β1 expression, VEGF-D secretion, proliferative, migratory/invasive capacities, latter functions being stimulated further with VEGF-D. The requirement of α9β1 for native and VEGF-D-stimulated proliferation, migration and Erk activation was demonstrated by treating with α9β1 blocking antibody or knock-down of α9. An autocrine role of VEGF-D in migration was shown by its impairment by silencing VEGF-D and restoration with VEGF-D. 468LN cells and their soluble products stimulated tube formation, migration/invasiveness of HMVEC-dLy cell in a VEGF-D dependent manner as indicated by the loss of stimulation by silencing VEGF-D in 468LN cells. Furthermore, 468LN cells showed α9-dependent stimulation of migration/invasiveness by macrophage products. Finally, capacity for intra-tumoral lymphangiogenesis and lymphatic metastasis in nude mice was completely abrogated by stable knock-down of either VEGF-D or α9 in 468LN cells. CONCLUSION: Differential capacity for VEGF-D production and α9β1 integrin expression by 468LN cells jointly contributed to their lymphatic metastatic phenotype

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Study of Quasielastic scattering for 7Li+159Tb at around- barrier energies

Quasielastic scattering cross sections for the reaction 7Li+159Tb have been measured at large backangles, at energies around the Coulomb barrier. The quasielastic barrier distribution has been extracted from the measured quasielastic scattering excitation function, including and excluding α particle contribution. The peak of the quasielastic barrier distribution including α particle contribution shows a shift towards higher energy compared to the peak of the distribution without α particles. The quasielastic barrier distribution when compared to the calculated fusion barrier distribution, appears to show reasonable agreement for the system

Study of Quasielastic scattering for

Quasielastic scattering cross sections for the reaction 7Li+159Tb have been measured at large backangles, at energies around the Coulomb barrier. The quasielastic barrier distribution has been extracted from the measured quasielastic scattering excitation function, including and excluding α particle contribution. The peak of the quasielastic barrier distribution including α particle contribution shows a shift towards higher energy compared to the peak of the distribution without α particles. The quasielastic barrier distribution when compared to the calculated fusion barrier distribution, appears to show reasonable agreement for the system

Study of Quasielastic scattering for 7Li+159Tb at around- barrier energies

Quasielastic scattering cross sections for the reaction 7Li+159Tb have been measured at large backangles, at energies around the Coulomb barrier. The quasielastic barrier distribution has been extracted from the measured quasielastic scattering excitation function, including and excluding α particle contribution. The peak of the quasielastic barrier distribution including α particle contribution shows a shift towards higher energy compared to the peak of the distribution without α particles. The quasielastic barrier distribution when compared to the calculated fusion barrier distribution, appears to show reasonable agreement for the system