Solid tumors carry out the formation of new vessels providing blood supply for growth, tumor maintenance, and metastasis. Several processes take place during tumor vascularization. In angiogenesis, new vessels are derived from endothelial cells of pre-existing vessels; while in vasculogenesis, new vessels are formed de novo from endothelial progenitor cells, creating an abnormal, immature, and disorganized vascular network. Moreover, highly aggressive tumor cells form structures similar to vessels, providing a pathway for perfusion; this process is named vasculogenic mimicry (VM), where vessel-like channels mimic the function of vessels and transport plasma and blood cells. VM is developed by numerous types of aggressive tumors, including ovarian carcinoma which is the second most common cause of death among gynecological cancers. VM has been associated with poor patient outcome and survival in ovarian cancer, although the involved mechanisms are still under investigation. Several signaling molecules have an important role in VM in ovarian cancer, by regulating the expression of genes related to vascular, embryogenic, and hypoxic signaling pathways. In this review, we provide an overview of the current knowledge of the signaling molecules involved in the promotion and regulation of VM in ovarian cancer. The clinical implications and the potential benefit of identification and targeting of VM related molecules for ovarian cancer treatment are also discussed.

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Tissue contrast is a major challenge in the application of computed tomography (CT) and microcomputed tomography (micro-CT) techniques for imaging cancer. Contrast medium is used in order to enhance contrast of certain organs of interest, as well as tumors. Several types of contrast media have been used to assess tumor vasculature, perfusion and angiogenesis in preclinical studies. In general, low molecular weight contrast media have been used to characterize the first pass vascular dynamics of tumors with fast CT systems, while blood pool agents have been preferred to explore the delayed vascular dynamics with micro-CT systems. Together, these approaches provide qualitative, semi-quantitative, and quantitative information of the vascular architecture and vascular functionality of tumors in the preclinical scenario. Herein, we present an overview of contrast media, imaging techniques, image analysis methods, and quantitative parameters that have been used to evaluate tumor angiogenesis in vivo in recent preclinical studies. Preclinical applications on lesion detection and characterization, evaluation of vascular parameters as prognostic and predictive biomarkers, and evaluation of treatment response are also reviewed. These applications have demonstrated the potential of contrast-enhanced x-ray imaging to provide, in a noninvasive manner, a landscape of the spatial and temporal heterogeneity of the angiogenic process underlying tumor development.

The aim of this work was to systematically obtain quantitative imaging parameters with static and dynamic contrast-enhanced (CE) X-ray imaging techniques and to evaluate their correlation with histological biomarkers of angiogenesis in a subcutaneous C6 glioma model. Enhancement (E), iodine concentration (CI), and relative blood volume (rBV) were quantified from single- and dual-energy (SE and DE, respectively) micro-computed tomography (micro-CT) images, while rBV and volume transfer constant (Ktrans) were quantified from dynamic contrast-enhanced (DCE) planar images. CI and rBV allowed a better discernment of tumor regions from muscle than E in SE and DE images, while no significant differences were found for rBV and Ktrans in DCE images. An agreement was found in rBV for muscle quantified with the different imaging protocols, and in CI and E quantified with SE and DE protocols. Significant strong correlations (Pearson r > 0.7, p < 0.05) were found between a set of imaging parameters in SE images and histological biomarkers: E and CI in tumor periphery were associated with microvessel density (MVD) and necrosis, E and CI in the complete tumor with MVD, and rBV in the tumor periphery with MVD. In conclusion, quantitative imaging parameters obtained in SE micro-CT images could be used to characterize angiogenesis and necrosis in the subcutaneous C6 glioma model.