Melanoma Cells Use Thy-1 (CD90) on Endothelial Cells for Metastasis Formation

Abstract

The cell adhesion molecule Thy-1 (CD90) mediates the adhesion of melanoma cells to activated human endothelial cells (EC) via the interaction with the αvβ3-integrin on the tumor cells in vitro. Here, we report a strong expression of Thy-1 on both blood vessel and lymphatic EC in melanoma and melanoma metastases. Vascular endothelial growth factor and tumor necrosis factor-α were identified as inducers of Thy-1 expression on EC in vitro. The physiological role of Thy-1 for lymphogenic and hematogenic metastasis of melanoma cells was substantiated in an experimental metastasis model using B16/F10 melanoma cells. Mice lacking Thy-1 showed markedly diminished experimental lung metastasis after injection of B16/F10 melanoma cells compared to wild-type littermate controls. In addition, on generation of a primary subcutaneous tumor, metastasis to regional lymph nodes was clearly reduced in Thy-1(-/-) mice. However, Thy-1 deletion did not affect subcutaneous primary tumor growth, tumor-induced recruitment of inflammatory cells or T cells, angiogenesis, or T-cell activation. In conclusion, Thy-1 contributes to metastasis of melanoma cells by mechanisms likely involving a Thy-1-mediated adhesion of melanoma cells to EC.

The prognostic value of combination of CD90 and OCT4 for hepatocellular carcinoma after curative resection

“…To further determine the prognostic value of CD90, we analyzed relationships between CD90 and clinicopathologic parameters. We also found positive correlation between CD90 and several clinicopathologic parameters: pathological grade, satellite lesion and PVTT, which was consistent with the concept that CD90 promoted metastatic properties of tumors [12,29]. We divided HCC patients into two groups according to CD90 expression and discovered that it could be an independent predictor for prognosis.…”

“…In humans, it is mainly expressed on several types of cells including: broblasts, blood stem cells and activated microvascular endothelial cells (ECs) [9,10]. Nevertheless, high level of CD90 expression has also been observed in CAFs [11][12][13]. Sukowati et al [14] found that CAFs isolated from human HCC tissues were positive for CD90.…”

Neuronal NAMPT is Released after Cerebral Ischemia and Protects against White Matter Injury

“…We did not observe the presence of HA-tagged NAMPT within non-neuronal cells in the mouse brain ( Figure 1D), although Thy-1 has been reported to be expressed in endothelial cells and in white blood cells such as T lymphocytes, 21,22 two cell types that are intimately involved in the pathogenesis of ischemic stroke. However, T-cell infiltration into the brain usually occurs 3 days after cerebral ischemia, 23 whereas NAMPT already exerted WM protection effect within this timeframe in our studies.…”

Dynamic catch of a Thy-1–α5β1+syndecan-4 trimolecular complex

“…It has recently been reported that Thy-1 mediates melanoma cell adhesion to the endothelium, facilitating tumour metastasis in the B16/F10 model 12 . This interaction is mainly attributed to integrin a v b 3 engagement; however, the downstream signalling responses and adhesive phenotype of cells engaging Thy-1 are less well known.…”

“…Thy-1 also binds heparin sulphate proteoglycans (HSPGs), including syndecan-4 (Syn4), through a conserved polycationic motif in the C-C' strand loop motif 7,10 . In patients with metastatic melanoma, Thy-1 is highly expressed on both the venous and lymphatic endothelium, where it facilitates metastasis in experimental models of melanoma 11,12 . Thy-1 expression is also enriched on human tumour-associated endothelium and lymphatic vessels 13 .…”