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It has been reported that a polypeptide encoded by collagen type VI alpha 1 chain (COL6A1), one of the three α chains of type VI collagen, is strongly associated with the migration and invasion of highly metastatic human pancreatic cancer BxPC‑M8 cells and excessive proliferation of LNCaP cells. We previously reported that non‑triple helical type VI collagen α1 chain, NTH α1(VI), a non‑triple helical polypeptide encoded by COL6A1, is not derived from type VI collagen and exists in cancer cell‑conditioned media. Therefore, NTH α1(VI) may be involved in cancer cell migration, invasion, and proliferation. The active entity that promotes cellular behaviors in cancer remains unclear. Thus, we predicted that NTH α1(VI) has cancer‑promoting activity, such as the ability to induce cell proliferation. This study was conducted to examine whether NTH α1(VI) and/or its derived peptides are involved in cancer cell proliferation. Highly metastatic human pancreatic S2‑VP10 cells were used to explore the potential of COL6A1 knockdown in reducing cell proliferation. Moreover, S2‑VP10 conditioned medium was assessed after molecular size‑fractionation to determine whether the inhibitory effect of COL6A1 knockdown could be rescued by the medium. We showed that S2‑VP10‑conditioned medium contained COL6A1 polypeptide, but not COL6A2, suggesting that COL6A1 in the conditioned medium of S2‑VP10 cells reflects the presence of NTH α1(VI). COL6A1 knockdown repressed S2‑VP10 cell proliferation and this repression was rescued using the conditioned medium of S2‑VP10 cells. The fraction of conditioned medium containing peptides smaller than 10 kDa rescued the inhibitory effect; however, the fraction containing polypeptides larger than 10 kDa, including NTH α1(VI), did not show rescue activity, indicating that NTH α1(VI) fragmentation is necessary for enhanced cancer cell proliferation. In conclusion, fragmentation of NTH α1(VI) into peptides <10 kDa is required for its cancer cell proliferation‑promoting activity.


Takamichi Sato, Kazuhiro Tokunaka, Kan Saiga, Arihiro Tomura, Hidemitsu Sugihara, Toshihiko Hayashi, Yasutada Imamura, Makoto Morita. Involvement of non‑triple helical type VI collagen α1 chain, NTH α1(VI), in the proliferation of cancer cells. Oncology reports. 2020 Nov;44(5):2297-2305

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PMID: 33000277

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