Dual effects of collagenase-3 on melanoma: metastasis promotion and disruption of vasculogenic mimicry
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Xiulan Zhao1,2,*, Baocun Sun1,2,3,*, Yanlei Li2,*, Yanrong Liu2, Danfang Zhang1,2, Xudong Wang3, Qiang Gu1,2, Jianmin Zhao2, Xueyi Dong1,2, Zhiyong Liu3, Na Che1,2
1Department of Pathology, General Hospital of Tianjin Medical University, Tianjin, China
2Department of Pathology, Tianjin Medical University, Tianjin, China
3Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin, China
*These authors have contributed equally to this work
Baocun Sun, e-mail: [email protected]
Keywords: MMP-13, Melanoma, Vasculogenic mimicry, Laminin, VE-cadherin
Received: December 13, 2014 Accepted: January 23, 2015 Published: February 26, 2015
Vasculogenic mimicry (VM) is a functional microcirculation formed by tumor cells. Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, promote VM formation. Another specific MMP, collagenase-3 (MMP-13), has broad substrate specificity and potentially affects tumor metastasis and invasion. Here we found that MMP-13 was associated with metastasis and poor survival in 79 patients with melanoma. MMP-13 expression was inversely correlated with VM. These results were confirmed in human and mouse melanoma cell lines. We found that MMP-13 cleaves laminin-5 (Ln-5) into small fragments to accelerate tumor metastasis. Degradation of Ln-5 and VE-cadherin by MMP-13 inhibited VM formation. In conclusion, MMP-13 has a dual effect in melanoma, as it promotes invasion and metastasis but disrupts VM formation.
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