Activation of a procollagenase by low-molecular-weight angiogenesis factor

Abstract

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.

Potentiating effect of heparin in the activation of procollagenase by a low‐Mr angiogenesis factor

“…Analysis of the degradation products from the Gore-cat~ysed hydrolysis of Type-I collagen by SDS-polyacrylamide gel electrophoresis revealed the $95 and 3/o collagen fragments ~h~a~teristic of the action of mammalian collagenase 181. We have previously reported that ESAF activates a skin fibroblast procollagenase [3]. Here we have shown that heparin potentiates the action of limiting amounts of ESAF.…”

“…We have also shown that ESAF activates skin fibroblast pr~olla~~e [3]. A unifying mechanism of action for a factor which is able to induce both endotherm cell proliferation and directional growth, which are properties of a~ogenic substances [4], is difficult to understand.…”

“…The requirements for an angiogenesis factor are that it can stimulate endothelial cells to proliferate and also cause them to migrate towards the source of the factor. The directional effect could be partially explained by the activation by angiogenesis factors of procollagenase present in the connective tissue matrix [3]. Since the collagen in the intracellular matrix is in a fibrillar form, digestion would be limited, as the insoluble collagen is a relatively poor substrate for the enzyme [ 161.…”

Raised levels of latent collagenase activating angiogenesis factor (ESAF) are present in actively growing human intracranial tumours

“…It has been shown that ESAF activates latent collagenase (Weiss et al, 1983) by reversing the inhibition of this enzyme by tissue inhibitor of metalloproteinases (McLaughlin et al, 1991 (Table III). Samples were frozen at -20'C prior to extraction.…”

“…Assay of angiogenic material for its ability to activate latent collagenase was performed according to the method of Weiss et al (1983). Results were expressed as 1tg collagen degraded h-I mg-' protein in the supernatant.…”