Neovascularization is required for solid tumor maintenance, progression, and metastasis. The most described contribution of cancer cells in tumor neovascularization is the secretion of factors, which attract various cell types to establish a microenvironment that promotes blood vessel formation. The cancer stem cell hypothesis suggests that tumors are composed of cells that may share the differentiation capacity of normal stem cells. Similar to normal stem cells, cancer stem cells (CSCs) have the capacity to acquire different phenotypes. Thus, it is possible that CSCs have a bigger role in the process of tumor neovascularization. In this study, we show the capacity of a specific population of ovarian cancer cells with stem-like properties to give rise to xenograft tumors containing blood vessels, which are lined by human CD341 cells. In addition, when cultured in high-density Matrigel, these cells mimic the behavior of normal endothelial cells and can form vessel-like structures in 24 hours. Microscopic analysis showed extensive branching and maturation of vessel-like structures in 7 days. Western blot and flow cytometry analysis showed that this process is accompanied by the acquisition of classic endothelial markers, CD34 and VEcadherin. More importantly, we show that this process is vascular endothelial growth factor-independent, but IKKb-dependent. Our findings suggest that anti-angiogenic therapies should take into consideration the inherent capacity of these cells to serve as vascular progenitors.

PBX1 is a TALE homeodomain transcription factor involved in organogenesis and tumorigenesis. Although it has been shown that ovarian, breast, and melanoma cancer cells depend on PBX1 for cell growth and survival, the molecular mechanism of how PBX1 promotes tumorigenesis remains unclear. Here, we applied an integrated approach by overlapping PBX1 ChIP-chip targets with the PBX1-regulated transcriptome in ovarian cancer cells to identify genes whose transcription was directly regulated by PBX1. We further determined if PBX1 target genes identified in ovarian cancer cells were co-overexpressed with PBX1 in carcinoma tissues. By analyzing TCGA gene expression microarray datasets from ovarian serous carcinomas, we found co-upregulation of PBX1 and a significant number of its direct target genes. Among the PBX1 target genes, a homeodomain protein MEOX1 whose DNA binding motif was enriched in PBX1-immunoprecipicated DNA sequences was selected for functional analysis. We demonstrated that MEOX1 protein interacts with PBX1 protein and inhibition of MEOX1 yields a similar growth inhibitory phenotype as PBX1 suppression. Furthermore, ectopically expressed MEOX1 functionally rescued the PBX1-withdrawn effect, suggesting MEOX1 mediates the cellular growth signal of PBX1. These results demonstrate that MEOX1 is a critical target gene and cofactor of PBX1 in ovarian cancers.

HIV disproportionately impacts young Black men who have sex with men (YBMSM). Pre-exposure prophylaxis (PrEP) is an effective strategy that can avert new HIV infections in YBMSM. Barriers exist for YBMSM to access PrEP. We sought to determine factors associated with awareness of and willingness to take PrEP in a sample of YBMSM. Only 8% were currently on PrEP despite many (66%) reporting condomless anal sex, a recent provider visit (54%), disclosing their sexual orientation to their regular medical provider (62%), or a willingness to take PrEP (62%). In bivariate analysis, increased number of lifetime partners, current PrEP use, and disclosure of sexual orientation to a doctor were associated with awareness of PrEP, while condomless anal sex and higher perceived risk was associated with willingness to take PrEP. Sex with females was associated with lower willingness. Providers may be missing key opportunities to educate YBMSM about PrEP and incorporate PrEP into comprehensive sexual health care.

Despite high HIV rates among young Black men who have sex with men (YBMSM), there is limited data about condom use during first same-sex (FSS). This study sought to understand socio-contextual factors of 50 YBMSM age 15–19 that influenced condom use during FSS. Condom use was influenced by individual, partner and community factors. Individual factors: recent illness or STI promoted use, while frequent HIV testing prompted nonuse. Partner factors: partner’s proactively encouraging condoms, while trust and condom discomfort promoted nonuse. Larger community factors - presence of females were key for use, while limited sexual health information combined with peers who discouraged condoms prompted nonuse. A multi-level approach may be useful in developing sexual health programming for these young men.