Identification of CD24 as a marker for tumorigenesis of melanoma.

OBJECTIVE: Cutaneous melanoma (CM) is a common skin cancer. Surgery is still the primary treatment for CM, as melanoma is resistant to chemotherapy. In the recent years, it has been found that cancer stem-like cells (CSCs) are responsible for this drug resistance. CD24 is a widely used marker to isolate CSCs. In this study, we aimed to analyze the properties of CD24+ and CD24- subpopulation of melanoma cells. MATERIALS AND METHODS: We isolated CD24+ cells CSCs using magnetic-activated cell sorting system. We extracted total RNA and carried out reverse transcription polymerase chain reaction analysis. We counted the cell colonies using soft agar assay and assessed the cell invasion using cell migration assay. We implanted CD24+ or CD24- cells into the flank of non-obese diabetic severe combined immunodeficiency mice, and measured the tumor volumes every 5 days until the end of the experiment. We carried out immunohistochemical analysis to study the tissue sections. RESULTS: We demonstrated that the CD24+ subpopulation has self-renewal properties in vitro and in vivo by using soft agar assay and xenograft tumor model. Furthermore, we confirmed that CD24 expression is accompanied by activation of Notch1 signaling pathway. CONCLUSION: This study provides new knowledge on the role of CD24 in the tumorigenic ability of melanoma.

Prognostic significance of in situ and plasma levels of transforming growth factor ß1, -2 and -3 in cutaneous melanoma.

Melanoma is an aggressive type of cutaneous malignancy. Transforming growth factor (TGF)­ß has been demonstrated to be an important mediator of tumor progression. However, to the best of our knowledge, the systemic roles of plasma TGF­ß and TGF­ß in situ have not been investigated in Han Chinese melanoma patients. The results of the present study demonstrated that the in situ and plasma levels of TGF­ß1, TGF­ß2 and TGF­ß3 protein and messenger RNA were significantly elevated in tumor tissues compared with those of normal tissues. The survival rates of the patients which were triple­positive (TGF­ß1+, TGF­ß2+ and TGF­ß3+) were found to be markedly decreased compared to those which were single­ (TGF­ß1+, TGF­ß2+ or TGF­ß3+) or double­positive (TGF­ß1+, TGF­ß2+; TGF­ß2+, TGF­ß3+; or TGF­ß1+, TGF­ß3+). These results may therefore contribute to the use of TGF­ß as a prognostic biomarker, and to the development of novel therapies for melanoma treatment.

SUMO1 genetic polymorphisms may contribute to the risk of nonsyndromic cleft lip with or without palate: a meta-analysis.

OBJECTIVE: We conducted the present meta-analysis to investigate whether single-nucleotide polymorphisms (SNPs) in the SUMO1 gene contribute to the risk of nonsyndromic cleft lip with or without palate (NSCL/P). METHOD: The Web of Science (1945-2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966-2013), EMBASE (1980-2013), CINAHL (1982-2013), and the Chinese Biomedical Database (CBM) (1982-2013) were searched without language restrictions. Meta-analysis was performed with the use of the STATA statistical software. RESULTS: Six studies with a total of 1381 NSCL/P patients and 2054 control subjects were included. Twenty-seven functional polymorphisms in the SUMO1 gene were assessed. Our results indicated that SUMO1 genetic polymorphisms were correlated with an increased risk of NSCL/P. Subgroup analysis by the SNP type indicated that 4 functional polymorphisms (rs12470401 T>C, rs16838917 A>G, rs12470529 A>G, and rs7572505 A>G) in the SUMO1 gene might be strongly correlated with NSCL/P risk. Furthermore, ethnicity-stratified analysis demonstrated that SUMO1 genetic polymorphisms were closely related to an increased risk of NSCL/P among both Asians and Caucasians. CONCLUSION: Our findings provide empirical evidence that SUMO1 genetic polymorphisms might be strongly involved in the etiology of NSCL/P, especially for rs12470401 T>C, rs16838917 A>G, rs12470529 A>G, and rs7572505 A>G polymorphisms.

CD24 expression predicts poor prognosis for patients with cutaneous malignant melanoma.

Cutaneous malignant melanoma represents the major cause of mortality among skin cancers. Metastasis-associated protein CD24 is a small, heavily glycosylated cell surface protein that is overexpressed in various human malignancies. The present study was designed to determine the roles of CD24 in cutaneous malignant melanoma. The levels of CD24 mRNA and protein in cutaneous malignant melanoma tissues were detected by RT-PCR, Western blot and IHC. In patient samples, the levels of CD24 mRNA and protein were higher in cancer tissues than that in normal tissues. CD24 expression decreased the survival time of the patients with melanoma. Taken together, these results suggest that CD24 may be used as a new drug target for cutaneous malignant melanoma.

CSMD1 exhibits antitumor activity in A375 melanoma cells through activation of the Smad pathway.

In this work, we studied the effects of CUB and Sushi multiple domains 1 gene (CSMD1) expression in A375 melanoma cells in vivo and in vitro. CSDM1 expression decreased proliferation and migration, and increased apoptosis and G(1) arrest in A375 cells in vitro. Expression of CSDM1 in established xenografted tumors decreased tumor size and weight, and decreased the density of intratumor microvessels. The survival rate of mice with tumors expressing CSMD1 was significantly higher than mice with tumors that did not express CSDM1. These results confirm the role of CSDM1 as a tumor suppressor gene in melanoma cells. Furthermore, we found that CSMD1 can interact with Smad3, activate Smad1, Smad2, and Smad3, and increase the expression of Smad4. These results might prove helpful for the development of novel therapies for melanoma treatment.