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

Zhao X, Sun B, Li Y, Liu Y, Zhang D, Wang X, Gu Q, Zhao J, Dong X, Liu Z, Che N - Oncotarget (2015)

Bottom Line: 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.In conclusion, MMP-13 has a dual effect in melanoma, as it promotes invasion and metastasis but disrupts VM formation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, General Hospital of Tianjin Medical University, Tianjin, China.

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.

No MeSH data available.


Related in: MedlinePlus

MMP-13 induces nuclear translocation of β-catenin(A) Left panel: higher β-catenin+ levels in cytoplasm and nucleus are seen in melanoma tissues with high MMP-13 expression than in those with low MMP-13 expression. *P < 0.05, bar: 100 μm. (B) β-catenin immunofluorescence staining shows that adding MMP-13 to A375 cell culture medium induces dose-dependent nuclear translocation of β-catenin, from cell membranes in the untreated control group. Number of tumor cells with positive nuclear staining (red arrow) varies with MMP-13 concentration, which is most obvious at 2 μg/ml. *P < 0.05, compared with untreated controls (n = 3). Bar: 50 μm. (C) After 72 h stimulation with exogenous MMP-13, A375 melanoma cells show dose-dependent increase in MMP-13 mRNA.
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Figure 6: MMP-13 induces nuclear translocation of β-catenin(A) Left panel: higher β-catenin+ levels in cytoplasm and nucleus are seen in melanoma tissues with high MMP-13 expression than in those with low MMP-13 expression. *P < 0.05, bar: 100 μm. (B) β-catenin immunofluorescence staining shows that adding MMP-13 to A375 cell culture medium induces dose-dependent nuclear translocation of β-catenin, from cell membranes in the untreated control group. Number of tumor cells with positive nuclear staining (red arrow) varies with MMP-13 concentration, which is most obvious at 2 μg/ml. *P < 0.05, compared with untreated controls (n = 3). Bar: 50 μm. (C) After 72 h stimulation with exogenous MMP-13, A375 melanoma cells show dose-dependent increase in MMP-13 mRNA.

Mentions: The IHC staining results showed that cytoplasmic and nuclear localization were more easily detected in the high MMP-13high group, whereas membrane-bound β-catenin exhibited an opposite trend (Figure 6A). Exogenous addition of MMP-13 to the culture medium induced nuclear relocation of β-catenin in A375 in a dose-dependent manner (Figure 6B), and induced increased MMP-13 mRNA levels in A375 cells, which suggests a self-driven loop of MMP-13 production (Figure 6C).


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

Zhao X, Sun B, Li Y, Liu Y, Zhang D, Wang X, Gu Q, Zhao J, Dong X, Liu Z, Che N - Oncotarget (2015)

MMP-13 induces nuclear translocation of β-catenin(A) Left panel: higher β-catenin+ levels in cytoplasm and nucleus are seen in melanoma tissues with high MMP-13 expression than in those with low MMP-13 expression. *P < 0.05, bar: 100 μm. (B) β-catenin immunofluorescence staining shows that adding MMP-13 to A375 cell culture medium induces dose-dependent nuclear translocation of β-catenin, from cell membranes in the untreated control group. Number of tumor cells with positive nuclear staining (red arrow) varies with MMP-13 concentration, which is most obvious at 2 μg/ml. *P < 0.05, compared with untreated controls (n = 3). Bar: 50 μm. (C) After 72 h stimulation with exogenous MMP-13, A375 melanoma cells show dose-dependent increase in MMP-13 mRNA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496190&req=5

Figure 6: MMP-13 induces nuclear translocation of β-catenin(A) Left panel: higher β-catenin+ levels in cytoplasm and nucleus are seen in melanoma tissues with high MMP-13 expression than in those with low MMP-13 expression. *P < 0.05, bar: 100 μm. (B) β-catenin immunofluorescence staining shows that adding MMP-13 to A375 cell culture medium induces dose-dependent nuclear translocation of β-catenin, from cell membranes in the untreated control group. Number of tumor cells with positive nuclear staining (red arrow) varies with MMP-13 concentration, which is most obvious at 2 μg/ml. *P < 0.05, compared with untreated controls (n = 3). Bar: 50 μm. (C) After 72 h stimulation with exogenous MMP-13, A375 melanoma cells show dose-dependent increase in MMP-13 mRNA.
Mentions: The IHC staining results showed that cytoplasmic and nuclear localization were more easily detected in the high MMP-13high group, whereas membrane-bound β-catenin exhibited an opposite trend (Figure 6A). Exogenous addition of MMP-13 to the culture medium induced nuclear relocation of β-catenin in A375 in a dose-dependent manner (Figure 6B), and induced increased MMP-13 mRNA levels in A375 cells, which suggests a self-driven loop of MMP-13 production (Figure 6C).

Bottom Line: 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.In conclusion, MMP-13 has a dual effect in melanoma, as it promotes invasion and metastasis but disrupts VM formation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, General Hospital of Tianjin Medical University, Tianjin, China.

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.

No MeSH data available.


Related in: MedlinePlus