Dual effects of collagenase-3 on melanoma: metastasis promotion and disruption of vasculogenic mimicry.
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.
Department of Pathology, General Hospital of Tianjin Medical University, Tianjin, China.|Department of Pathology, Tianjin Medical University, Tianjin, China.
Xiulan
X
Zhao
Department of Pathology, General Hospital of Tianjin Medical University, Tianjin, China.|Department of Pathology, Tianjin Medical University, Tianjin, China.|Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin, China.
Baocun
B
Sun
Department of Pathology, Tianjin Medical University, Tianjin, China.
Yanlei
Y
Li
Department of Pathology, Tianjin Medical University, Tianjin, China.
Yanrong
Y
Liu
Department of Pathology, General Hospital of Tianjin Medical University, Tianjin, China.|Department of Pathology, Tianjin Medical University, Tianjin, China.
Danfang
D
Zhang
Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin, China.
Xudong
X
Wang
Department of Pathology, General Hospital of Tianjin Medical University, Tianjin, China.|Department of Pathology, Tianjin Medical University, Tianjin, China.
Qiang
Q
Gu
Department of Pathology, Tianjin Medical University, Tianjin, China.
Jianmin
J
Zhao
Department of Pathology, General Hospital of Tianjin Medical University, Tianjin, China.|Department of Pathology, Tianjin Medical University, Tianjin, China.
Xueyi
X
Dong
Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin, China.
Zhiyong
Z
Liu
Department of Pathology, General Hospital of Tianjin Medical University, Tianjin, China.|Department of Pathology, Tianjin Medical University, Tianjin, China.
Na
N
Che
D000328:Adult; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007797:Laminin / Q000378:metabolism; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000502:physiology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008545:Melanoma / Q000098:blood supply* / Q000201:enzymology / Q000401:mortality / Q000556:secondary*; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D008833:Microcirculation; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
C400567:LAMC2 protein, human; D007797:Laminin; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2
MMP-13; VE-cadherin; laminin; melanoma; vasculogenic mimicry