Radiofrequency Irradiation Mitigated UV-B-Induced Skin Pigmentation by Increasing Lymphangiogenesis

Dermal macrophages containing melanin increase skin pigmentation since dermal melanin removal is slower than epidermal melanin removal. Lymphatic vessels are also involved in melanin clearance. We evaluated whether radiofrequency (RF) irradiation induced an increase in HSP90, which promotes lymphangiogenesis by activating the BRAF/MEK/ERK pathway and decreasing tyrosinase activity, in the UV-B exposed animal model. The HSP90/BRAF/MEK/ERK pathway was upregulated by RF. Tyrosinase activity and the VEGF-C/VEGFR 3/PI3K/pAKT1/2/pERK1/2 pathway, which increase lymphangiogenesis, as well as the expression of the lymphatic endothelial marker LYVE-1, were increased by RF. Additionally, the number of melanin-containing dermal macrophages, the melanin content in the lymph nodes, and melanin deposition in the skin were decreased by RF. In conclusion, RF increased HSP90/BRAF/MEK/ERK expression, which decreased tyrosinase activity and increased lymphangiogenesis to eventually promote the clearance of dermal melanin-containing macrophages, thereby decreasing skin pigmentation.

Tumor Endothelial Marker 8 Promotes Proliferation and Metastasis via the Wnt/β-Catenin Signaling Pathway in Lung Adenocarcinoma

Tumor endothelial marker 8 (TEM8), also known as ANTXR1, was highly expressed in cancers, and was identified as a biomarker for early diagnosis and prognosis in some cancers. However, the clinical role and molecular mechanisms of TEM8 in lung adenocarcinoma (LUAD) are still unclear. The present study aimed to explore its clinical value and the molecular mechanisms of TEM8 underlying the progression of LUAD. Our study found the elevation of TEM8 in LUAD cell lines and tissues. What’s more, we observed that the TEM8 expression level was associated with tumor size, primary tumor, and AJCC stage, and LUAD patients with high TEM8 expression usually have a poor prognosis. Then, we conducted a series of experiments by the strategy of loss-of-function and gain-of-function, and our results suggested that the knockdown of TEM8 suppressed proliferation, migration, and invasion and induced apoptosis in LUAD whereas overexpression of TEM8 had the opposite effect. Molecular mechanistic investigation showed that TEM8 exerted its promoting effects mainly through activating the Wnt/β-catenin signaling pathway. In short, our findings suggested that TEM8 played a crucial role in the progression of LUAD by activating the Wnt/β-catenin signaling pathway and could serve as a potential therapeutic target for LUAD.

Evaluation of Lympho-vascular Invasion in Breast Carcinoma Using Lymphatic Endothelial Marker (D2-40)

Breast cancer has become the most frequently diagnosed cancer and the leading cause of cancer-related death among women worldwide, overtaking lung cancer. The Present study attempts to investigate the use of D2 -40 for the detection of lympho- vascular invasion in node negative breast cancer. Additionally the lympho-vascular invasion using D2 -40 and its association with distant metastasis and overall prognosis of the patient was also explored.

Abstract 13408: Tumor Endothelial Marker 1 is Upregulated in Cardiomyocytes and Participates in Cardiac Remodeling After Cardiac Injury

Background: Tumor endothelial marker 1 (TEM1), also known as endosialin or CD248, is a transmembrane protein that expresses in mesenchymal lineage-derived cells only during embryogenesis and becomes undetectable in normal tissues after birth. Re-expression of TEM1 is found on activated cells of mesenchymal lineage during pathological conditions, such as stroma cells in cancer, fibroblasts in organ fibrosis and wound healing, indicating its potential role in tissue remodeling and repair. The expression levels and physiological functions of TEM1 in heart are unknown. Methods and Results: All data were presented as mean ± standard error. In 2 explanted hearts from patients with heart failure (HF) received heart transplantation, immunofluorescence staining showed TEM1 was highly expressed in cardiomyocytes (CMs) and also in cardiac fibroblasts. In mouse HF models induced by intraperitoneal doxorubicin injection (5 mg/kg/wk for 4 wks) or coronary ligation, immunohistochemistry study showed TEM1 expression in hearts. Western blot showed 1.23±0.02 and 1.56±0.04-fold increase of cardiac TEM1 expression compared to controls, respectively. In vitro studies showed TEM1 expression increased in cultured CMs (H9C2 cells) treated with: (1) mechanical stretch (10% elongation at 60 cycles/min) (0 vs 0.5 vs 1 vs 3 hr, Western blot ratio: 1 vs 1.86±0.20 vs 1.87±0.20 vs 1.21±0.21, p<0.05), (2) doxorubicin (100 nM) (0 vs 0.5 vs 2 vs 4 hr: 1 vs 0.70±0.22 vs 1.75±0.26 vs 1.84±0.24, p<0.05) and (3) hypoxia (1% O2) (0 vs 0.5 vs 2 vs 4 hr: 1 vs 1.70±0.06 vs 1.49±0.22 vs 2.07±0.35, p<0.05). Recombinant TEM1 (rTEM1) promoted proliferation of H9C2 cells (saline vs rTEM1 50 vs 100 vs 250 nM, BrdU absorbance: 1.23±0.03 vs 1.36±0.03 vs 1.37±0.05 vs 1.38±0.02, p<0.05), reduced doxorubicin (1uM)-induced apoptosis (apoptosis ratio: 1 vs 0.89±0.02 vs 0.91±0.01 vs 0.88±0.05, p<0.05), increased cell hypertrophy (cell area ratio: 1 vs 1.11±0.21 vs 1.51±0.18 vs 1.63±0.13, p<0.05) and increased collagen production from CMs (collagen 3 Western blot ratio: 1 vs 1.49±0.15 vs 1.53±0.19 vs 1.29±0.24, p<0.05). Conclusions: Our study results indicate that TEM1 is upregulated in CMs after cardiac injury and influences the cell behaviors of CMs that related to cardiac remodeling.