Moreover, eccentric exercise is known to induce inflammatory responses such as leukocyte accumulation and up regulation of cytokines in exercised muscles. When considered together, these data provide an additional potential source and explanation for the increase in LG3 peptide in the urine of physically active mining workers. The LG3 peptide/endorepellin is among a number of proteolytic fragments from articular cartilage and basement membrane proteins which have anti-angiogenic/angiostatic effects. These include endostatin, tumstatin and arrestin, all Cterminal peptides derived from collagen XVIII and the a3 and a2 chains of collagen IV respectively. In support of our data, treadmill running exercise has been shown to transiently increase circulating levels of Reversine endostatin in healthy male subjects relative to individual levels of oxygen consumption, suggesting that endostatin reflects the level of physical exertion. Thus, it would be very interesting to ascertain if exposure to intensive physical activity also induces the release of either tumstatin or arresten peptides. Our results have shown that the LG3 peptide is elevated in the urine of physically active workers, and that a number of antiangiogenic peptides are known to be released from matrix proteins present in articular cartilage and/or in response to inflammatory cues or exercise. As such, we would like to propose our own ����provocative hypothesis���� in the spirit of that postulated by Mongiat et al.. It is possible that the physical activity induced release of LG3 peptide/endorepellin, and other similar anti-angiogenic fragments of ECM components, may be one of the physiological mechanisms for the well documented but still not clearly understood link between physical activity and reduced cancer risk or improved survival from cancer. Indeed, recombinant human endorepellin administration to the peritoneal cavity of nude mice or C57BL/6 mice inoculated with A431 human squamous cell carcinoma cells or Lewis lung carcinoma, respectively, restricted tumour development by specific disruption of tumour neovasculature. This resulted in tumour hypoxia, reduced proliferation, metabolism and increased tumour cell apoptosis. In addition, endostatin, tustatin and arresten have all been shown to inhibit tumour development in various model systems. While our proposed hypothesis remains to be tested, it is also important to address a number of limitations in our study. Firstly, the association between urinary LG3 peptide and physically active mining workers was observed in a small sample population and is therefore quite preliminary in ASP1517 nature and requires further validation in controlled laboratory settings with larger cohorts.