3D tumor angiogenesis models: recent advances and challenges

Abstract

The development of blood vessels, referred to as angiogenesis, is an intricate process regulated spatially and temporally through a delicate balance between the qualitative and quantitative expression of pro and anti-angiogenic molecules. As angiogenesis is a prerequisite for solid tumors to grow and metastasize, a variety of tumor angiogenesis models have been formulated to better understand the underlying mechanisms and associated clinical applications. Studies have demonstrated independent mechanisms inducing angiogenesis in tumors such as (a) HIF-1/VEGF mediated paracrine interactions between a cancer cell and endothelial cells, (b) recruitment of progenitor endothelial cells, and (c) vasculogenic mimicry. Moreover, single-cell sequencing technologies have indicated endothelial cell heterogeneity among organ systems including tumor tissues. However, existing angiogenesis models often rely upon normal endothelial cells which significantly differ from tumor endothelial cells exhibiting distinct (epi)genetic and metabolic signatures. Besides, the existence of intra-individual variations necessitates the development of improved tumor vascular model systems for personalized medicine. In the present review, we summarize recent advancements of 3D tumor vascular model systems which include (a) tissue engineering-based tumor models; (b) vascular organoid models, and (c) organ-on-chips and their importance in replicating the tumor angiogenesis along with the associated challenges to design improved models.

Organoids revealed: morphological analysis of the profound next generation in-vitro model with artificial intelligence

“…Optical, electrochemical, and other methods that can detect multiple indicators of organoids in vivo are still lacking. Therefore, studies with multi-disciplinary research are important future directions [ 131 , 132 ]. One promising approach is to use DL methods such as object detection and image segmentation to evaluate multiple indicators of organoids.…”

KLK3 in the Regulation of Angiogenesis—Tumorigenic or Not?

“…We foresee that the modern three-dimensional tumor angiogenesis models would be useful for the elucidation of the role of KLK3 in tumor angiogenesis. Such models incorporate, with cancer cells, tumor microenvironment, including extracellular matrix, and endothelial and other stromal cells, or their progenitor cells [124][125][126][127]. However, for the most part, such models remain to be established for studies of prostate cancer angiogenesis.…”

Molecular and Immune Phenotypic Modifications during Metastatic Dissemination in Lung Carcinogenesis

“…A significant factor in tumor cell dissemination is the formation of new blood vessels via angiogenesis in order to support tumor growth and expansion. VEGF is the main coordinator of new blood vessel formation from pre-existing endothelial cells on blood vessels [ 53 ]. Tumor cells and DTCs inside the hypoxic TME secrete high levels of pro-angiogenic factors such as basic fibroblast growth factor (bFGF), VEGF, PDGF-B, and TGF-β, which are key factors in juvenile vascular network formation in tumors [ 54 ].…”