[The mechanisms of microenvironments influence on vasculogenic mimicry between intraocular and subcutaneous melanoma].
OBJECTIVE
To investigate the influence of different microenvironments on melanoma vasculogenic mimicry, invasiveness and metastasis behavior.


METHODS
It was an experimental study. Sixty C57BL/6J mice were randomly divided into two groups with 30 mice per group. Melanoma B16 cells were injected into the subretinal space and groin area of mice synchronously. The number of each type of microcirculation pattern was counted. The invasion and metastasis were observed. EphA2, MMP-2 and MMP-9 expression and their mRNA levels were detected by immunohistochemical staining and real time RT-PCR and compared between two groups.


RESULTS
Five invasions and six lung metastases were found in the subretinal group while no invasion and metastasis were found in the groin group. The number of VM channels was significantly higher in subretinal group (t = 4. 188, P = 0.000). However, no significant difference of mosaic vessel and endothelium-dependent vessel was observed between two groups (t = 1.473, 1.805; P = 0.146, 0.076, respectively). EphA2, MMP-2 and MMP-9 expression was significantly higher in the subretinal group (data not shown). The mRNA levels of EphA2, MMP-2 and MMP-9 were rather higher in the subretinal tumor (t = 3.642, 8.109, 9.357; P = 0.002, 0.001 and 0.001, respectively). There was a positive association in melanoma cells of the VM between expression of EphA2 (r = 0.412, P = 0.021) but no statistically significant correlation between VM and MMP-2 (P > 0.05), nor between VM and MMP-9.


CONCLUSIONS
Different microenvironments affect invasiveness and blood supply patterns of melanoma. Melanoma cells in intraocular microenvironment increased EphA2 expression which induced the formation of VM channels. Moreover, the expression of MMP-2 and MMP-9 in tumor tissue increased to enhance the invasiveness and metastasis behavior.
Chen
Lu-Xia
LX
Eye Center of Tianjin Medical University, Tianjin 300070, China.
Sun
Bao-Cun
BC
Zhang
Shi-Wu
SW
He
Yan-Jin
YJ
Li
Xiao-Rong
XR
He
Zhong-Jiang
ZJ
D000818:Animals; D005260:Female; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008545:Melanoma / Q000098:blood supply* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D009366:Neoplasm Seeding; D009389:Neovascularization, Pathologic; D036104:Receptor, EphA2 / Q000378:metabolism
D036104:Receptor, EphA2; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse