RESUMO
Avascular tumours have the ability to establish a blood supply for themselves by secreting a humoral factor which stimulates their host's endothelial cells to proliferate and to migrate towards the tumour source. The mechanism of action of such a humoral angiogenesis factor is more than that of an endothelial-cell growth factor since it requires an oriented migration of cells towards the tumour. We report here the activation of pure skin-fibroblast procollagenase by a low-molecular-weight angiogenesis factor capable of stimulating endothelial-cell growth in vitro. The activation was observed when either Type I or III collagen was used as substrate. It is suggested that at least one function of angiogenesis factor is to promote limited degradation of the connective tissue through which it passes causing channeling in the matrix along which stimulated endothelial cells may migrate.
Assuntos
Indutores da Angiogênese/farmacologia , Colagenases , Precursores Enzimáticos/biossíntese , Substâncias de Crescimento/farmacologia , Colagenase Microbiana/biossíntese , Endotélio/citologia , Ativação Enzimática/efeitos dos fármacos , Fibroblastos/enzimologia , Humanos , Peso Molecular , Pele/enzimologiaRESUMO
Changes in the macromolecular matrix of the intervertebral disc may predispose to biomechanical failure of the disc. Such changes would involve extracellular enzymes capable of altering the collagen and proteoglycan of the disc matrix. In this study, extracts from homogenates of both annuli fibrosi and nuclei pulposi of human lumbar discs were found to contain neutral collagenolytic, gelatinolytic, and elastinolytic enzymes in all samples assayed. The specific activity of the collagenase was higher in extracts from nuclear than from annular tissue, a difference not seen with gelatinase or elastase. The collagenase was present as both a latent and active enzyme, the other enzymes being fully active. Human intervertebral discs therefore contain enzymes capable of degrading their extracellular macromolecular matrix.