Dual effects of collagenase-3 on melanoma: metastasis promotion and disruption of vasculogenic mimicry

// Xiulan Zhao 1, 2, * , Baocun Sun 1, 2, 3, * , Yanlei Li 2, * , Yanrong Liu 2 , Danfang Zhang 1, 2 , Xudong Wang 3 , Qiang Gu 1, 2 , Jianmin Zhao 2 , Xueyi Dong 1, 2 , Zhiyong Liu 3 , Na Che 1, 2 1 Department of Pathology, General Hospital of Tianjin Medical University, Tianjin, China 2 Department of Pathology, Tianjin Medical University, Tianjin, China 3 Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin, China * These authors have contributed equally to this work Correspondence to: Baocun Sun, e-mail: sunbaocun@aliyun.com Keywords: MMP-13, Melanoma, Vasculogenic mimicry, Laminin, VE-cadherin Received: December 13, 2014      Accepted: January 23, 2015      Published: February 26, 2015 ABSTRACT 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.