Stimulation of tumour growth by wound-derived growth factors

Abstract

Summar yThe goal of this work was to determine the molecular basis for the induction of tumour vascularization and progression by injury. Magnetic resonance imaging (MRI) studies demonstrated that administration of wound fluid derived from cutaneous injuries in pigs reduced the lag for vascularization and initiation of growth of C6 glioma spheroids, implanted in nude mice, and accelerated tumour doubling time. The former effect can be attributed to the angiogenic capacity of wound fluid as detected in vivo by MRI, and in vitro in promoting endothelial cell proliferation. The latter effect, namely the induced rate of tumour growth, is consistent with the angiogenic activity of wound fluid as well as with the finding that wound fluid was directly mitogenic to the tumour cells, and accelerated growth of C6 glioma in spheroid culture. Of the multiple growth factors present in wound fluid, two key factors, heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) and platelet-derived growth factor (PDGF), were identified as the dominant mitogens for C6 glioma, and inhibition of their activity using specific neutralizing antibodies suppressed the mitogenic effect of wound fluid on DNA synthesis in C6 glioma. This study suggests that the stimulatory effect of injury on tumour progression can possibly be attenuated by therapeutic targeting directed against a limited number of specific growth factors.

The relationship between the systemic inflammatory response and survival in patients with transitional cell carcinoma of the urinary bladder

“…However, it is known that as part of the systemic inflammatory response to the tumour there is a release of proinflammatory cytokines and growth factors, which not only stimulate tumour growth (Abramovitch et al, 1999;Coussens and Werb, 2002) but also produce profound catabolic effects on host metabolism (Kotler, 2000). For example, interleukin-6, produced by the tumour or infiltrating inflammatory cells, is recognised as a growth promoter in bladder cancer (Okamoto et al, 1997;Andrews et al, 2002).…”

Evaluation of a cumulative prognostic score based on the systemic inflammatory response in patients undergoing potentially curative surgery for colorectal cancer

“…The mechanism by which a systemic inflammatory response might influence cancer survival is not clear. However, it is known that as part of the systemic inflammatory response, there is a release of pro-inflammatory cytokines and growth factors which may promote tumour growth (Abramovitch et al, 1999) and compromise immune function (Coussens and Werb, 2002).…”

The systemic inflammatory response, weight loss, performance status and survival in patients with inoperable non-small cell lung cancer

“…However, it is known that as part of the systemic inflammatory response, there is a release of pro-inflammatory cytokines and growth factors (Fearon et al, 1991;Moldawer and Copeland, 1997) some of which produce metabolic disturbances (McMillan et al, 1994;Barber et al, 2000) and loss of lean tissue . The presence of these factors may also promote tumour growth (Moldawer and Copeland, 1997;Abramovitch et al, 1999) which, in turn, may further stimulate the systemic inflammatory response.…”