Effects of radiation on tumor vasculature

Abstract

Radiation has been utilized as a direct cytotoxic tumorcidal modality, however, the effect of radiation on tumor vasculature influences response to anticancer therapies.Although numerous reports have demonstrated vascular changes in irradiated tumors, the findings and implications are extensive and at times contradictory depending on the radiation dose, timing, and models used. In this review, we focus on the radiation-mediated effects on tumor vasculature with respect to doses used, timing postradiation, vasculogenesis, adhesion molecule expression, permeability, and pericyte coverage, including the latest findings.

Estimating quantitative physiological and morphological tissue parameters of murine tumor models using hyperspectral imaging and optical profilometry

“…Lower scattering parameters for tumors could be related to the structural changes within the diseased tissue, such as the local collagen fiber reorganization and alignment and cell and nuclei sizes [60]. However, the tumor oxygenation is expected to be lower than in the healthy tissue due to the increased demand for oxygen and disrupted supply, which opposes our findings [1][2][3]. A potential explanation is that the oxygen supply in small tumor models is sufficient to meet the growing tumor demand, as reported by Ziemer et al [61].…”

“…These properties might include but are not limited to physiological parameters such as melanin volume fraction and tissue oxygenation. The former is usually high in melanoma tumors [65]; the latter is often low in tumors and even lower in highly aggressive phenotypes [3]. Different tumor models could also be discriminated based on morphological properties such as graininess of the surface or highly tortuous and porous blood vessel structure [3][4][5].…”

“…Cancer cells require large amounts of nutrients and oxygen and therefore induce angiogenesis, the formation of new blood vessels, to meet the increased demand. Unlike in normal tissue, the blood vessels in tumor tissue are immature, tortuous and highly disorganized, resulting in hyperpermeability (leakage), low perfusion, hypoxia (deprivation of oxygen) and decreased blood flow within the tumor [3].…”

Treatment-associated remodeling of the pancreatic cancer endothelium at single-cell resolution

“…Furthermore, consistent with prior studies demonstrating that moderate and high doses (>2 GyE) of radiation inhibit angiogenesis, the DE analysis revealed downregulation of VWF and ANGPT2 and concomitant enrichment of IL6 and IL6R (13) (Figure 1F). In lieu of local angiogenesis, new vessel formation to support tumor recurrence after moderate-and high-dose radiation is dependent on vasculogenesis from bone marrow-derived cells (13). Lineage Program 5 ECs are enriched in CSF1 and CCL2, two factors that can increase the recruitment of tumor-associated macrophages that facilitate vasculogenesis (13).…”

“…In lieu of local angiogenesis, new vessel formation to support tumor recurrence after moderate-and high-dose radiation is dependent on vasculogenesis from bone marrow-derived cells (13). Lineage Program 5 ECs are enriched in CSF1 and CCL2, two factors that can increase the recruitment of tumor-associated macrophages that facilitate vasculogenesis (13). Radiation also enhances microvascular permeability in a dose-dependent manner, in part mediated by RhoA and Rho-associated kinases that regulate actin cytoskeletal organization and modulate the integrity of cell-cell junctions; the Lineage Program 5 differential expression analysis demonstrated an enrichment in both RHOA and ROCK2 (Figure 1F).…”