Generation of non-permissive basement membranes by anti-laminin antibody fragments produced by matrix-embedded gene-modified cells.
Tumor-induced blood vessel formation is a key process for the growth and spread of solid tumors, traditionally attributed to activated host endothelial cells (angiogenesis). Recently, highly aggressive cancer cells have been shown to form vascular channels in the absence of endothelial cells (vasculogenic mimicry). In this work, we have focused on the common dependence of both processes in their interactions with the surrounding extracellular matrix. We had previously described a human recombinant anti-laminin antibody that blocked the capillary morphogenesis of human endothelial cells. Here, we demonstrate that the purified antibody is capable of inhibiting channel formation by human cancer cells, suggesting a common morphogenic pathway in both processes. Moreover, matrix-embedded cells producing antibody fragments may render the surrounding matrix non-permissive for aggressive tumor cells. These results open the way for the development of new therapeutic strategies for cancer.
Sanz
Laura
L
Department of Immunology, Hospital Universitario Clínica Puerta de Hierro, San Martín de Porres 4, 28035 Madrid, Spain.
Feijóo
Mónica
M
Blanco
Belén
B
Serrano
Antonio
A
Alvarez-Vallina
Luis
L
D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology*; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism* / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000502:physiology; D006801:Humans; D007128:Immunoglobulin Fragments / Q000494:pharmacology*; D007797:Laminin / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D018613:Microscopy, Confocal; D009369:Neoplasms / Q000098:blood supply* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control*; D011509:Proteoglycans / Q000737:chemistry / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004338:Drug Combinations; D016326:Extracellular Matrix Proteins; D007128:Immunoglobulin Fragments; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen