Production of non-triple-helical collagen polypeptides under hypoxia and the implication for tumour

Non-triple-helical collagen polypeptides (NTHs) are alternative gene products lacking the typical collagen triple-helical structure. This study investigated NTH production in tumour cells and tissues. NTH α1(IV) was detected in various human tumour cell lines and extracted from human lung cancer tissues and tumours in mice. NTH production was significantly affected by serum concentration and occurred under hypoxic or hypoxia-mimetic conditions, even with sufficient ascorbic acid. This suggests NTHs are produced under physiological hypoxia, potentially contributing to tumour angiogenesis. NTH production generally coincided with hypoxia-inducible factor-1α (HIF-1α) accumulation, except with cobalt chloride, indicating HIF-1α is not directly involved in NTH α1(IV) production. NTH electrophoretic mobility on SDS-PAGE was higher under hypoxia or deferoxamine treatment, likely due to suppressed lysyl hydroxylase 3 activity. This study demonstrates NTH production in tumour cells and tissues under hypoxia, suggesting their association with tumour angiogenesis and potential as therapeutic targets.