[The influence of different microenvironments on melanoma invasiveness and microcirculation patterns].
OBJECTIVE
To investigate the influence of different microenvironments on tumor microcirculation patterns and invasive capability.


METHODS
Melanoma B16 cells were injected into the peritoneal cavity and skeletal muscle of C57 mice synchronously. CK18 expression in melanoma was assessed to distinguish the malignant phenotype of tumors in the peritoneal cavity from that in the skeletal muscle. HIF-1alpha, MMP-2 and MMP-9 protein and mRNA expression were compared in the two microenvironments. Cells positive for each immunohistochemical stain and the vessels representative of each type of microcirculation pattern were evaluated in two microenvironments.


RESULTS
CK18 and HIF-1alpha expression in melanoma were significantly higher in the skeletal muscle than in the peritoneal cavity (t = 8.142, t = 3.645, P < 0.05). Compared with the peritoneal cavity, melanoma cells in the skeletal muscle overexpressed MMP-2 and MMP-9 (t = 4.916, t = 7.782, P < 0.05). Real time-PCR results also showed that MMP-2 and MMP-9 mRNA levels in melanoma were higher in the skeletal muscle than in the peritoneal cavity (t = 36.814, t = 26.025, P < 0.05). Vasculogenic mimicry channels and endothelium-dependent vessels were the major microcirculation patterns in the skeletal muscle and in the peritoneal cavity respectively.


CONCLUSIONS
Different microenvironments affect invasiveness and blood supply patterns of melanoma. Different microenvironment induced tumor cell secretion of more invasion-related proteins and affect invasiveness and blood supply patterns of melanoma.
Zhang
Shi-Wu
SW
Department of Pathology, Tianjin Medical University Cancer Hospital, Tianjin, China. zhangshiwu666@yahoo.com.cn
Sun
Bao-Cun
BC
Zhang
Dan-Fang
DF
Li
Yan
Y
Rong
Zhe
Z
Zhao
Xiu-Lan
XL
D000818:Animals; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008545:Melanoma / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D010529:Peritoneal Cavity / Q000098:blood supply / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse