Collagen triple helix repeat containing 1 promotes tumor angiogenesis in gastrointestinal stromal tumors

Fu,Seng  Wang; Chen,Hai  Ying; Lin,Xiao  Lu; Yang,Li; Ge,Zhi  Zheng

doi:10.3892/ol.2017.7111

Collagen triple helix repeat containing 1 promotes tumor angiogenesis in gastrointestinal stromal tumors

Authors:
- Seng Wang Fu
- Hai Ying Chen
- Xiao Lu Lin
- Li Yang
- Zhi Zheng Ge
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Affiliations: Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao‑Tong University, Shanghai 200001, P.R. China
Published online on: October 2, 2017 https://doi.org/10.3892/ol.2017.7111
Pages: 7499-7505

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Abstract

Collagen triple helix repeat containing 1 (Cthrc1) is a secreted protein that has been observed to lead to poorer prognosis by inducing the invasion and metastasis in different tumors; however, it has not been demonstrated that Cthrc1 is involved in tumor angiogenesis. Immunohistochemical staining of Cthrc1 and CD31 in gastrointestinal stromal tumor tissue demonstrated that Cthrc1 is associated with microvascular density. Overexpression of Cthrc1 protein may alter the properties of human umbilical vein endothelial cells (HUVECs), including migration, invasion, tubule formation and aortic ring sprouting. Small interfering RNA‑mediated knockdown of Cthrc1 was performed to verify the opposite effects. Migration and tubule formation induced by Cthrc1 overexpression in HUVECs was attenuated by inhibition of phosphorylation in extracellular‑signal‑regulated protein kinase (ERK) and c‑Jun N‑terminal kinase (JNK) signaling pathways. The pro‑angiogenic effect of Cthcr1 is associated with increased phosphorylation of ERK and JNK in HUVECs. Silencing the expression of Cthrc1 protein may be a promising strategy to inhibit tumor angiogenesis.

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