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

Xiulan Zhao; Baocun Sun; Yanlei Li; Yanrong Liu; Danfang Zhang; Xudong Wang; Qiang Gu; Jianmin Zhao; Xueyi Dong; Zhiyong Liu; Na Che

doi:10.18632/oncotarget.3189

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Research Papers:

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

Xiulan Zhao, Baocun Sun _, Yanlei Li, Yanrong Liu, Danfang Zhang, Xudong Wang, Qiang Gu, Jianmin Zhao, Xueyi Dong, Zhiyong Liu and Na Che

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Oncotarget. 2015; 6:8890-8899. https://doi.org/10.18632/oncotarget.3189

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Abstract

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

Correspondence to:

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

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.

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Research Papers:

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

Abstract