Vascular patterns provide therapeutic targets in aggressive neuroblastic tumors

Abstract

Angiogenesis is essential for tumor growth and metastasis, nevertheless, in NB, results between different studies on angiogenesis have yielded contradictory results. An image analysis tool was developed to characterize the density, size and shape of total blood vessels and vascular segments in 458 primary neuroblastic tumors contained in tissue microarrays. The results were correlated with clinical and biological features of known prognostic value and with risk of progression to establish histological vascular patterns associated with different degrees of malignancy. Total blood vessels were larger, more abundant and more irregularly-shaped in tumors of patients with associated poor prognostic factors than in the favorable cohort. Tumor capillaries were less abundant and sinusoids more abundant in the patient cohort with unfavorable prognostic factors. Additionally, size of post-capillaries & metarterioles as well as higher sinusoid density can be included as predictive factors for survival. These patterns may therefore help to provide more accurate pre-treatment risk stratification, and could provide candidate targets for novel therapies.

Tumor Microenvironment Heterogeneity: A Review of the Biology Masterpiece, Evaluation Systems, and Therapeutic Implications

“…This study was extended to a cohort of more than 500 samples where a stiffer, crosslinked and less porous ECM was mainly found in unfavorable tumors [143,144]. Additionally, unfavorable tumors presented a highly vascularized ECM with mostly sinusoid vessels with abnormal morphologies [145]. Some ECM elements morphometric features helped the description of an ultra-high risk subgroup which could beneficiate of novel therapies [146].…”

Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line

“…We previously de ned an aggressive pattern of rigid ECMs in high-risk NB (HR-NB) [18]. NB stiff ECM is rich in cross-linked collagen III bers, poor in glycosaminoglycans, supporting sinusoidal vascular structures (blood and lymphatic) and with a high quantity of territorial vitronectin (VN, located in the cytoplasmic compartment and in a thin layer around the tumor cells) [19][20][21][22]. NB stiff ECM is also rich in collagen I bers and bronectin but in lesser amounts and with a more physiologicallike topology than collagen III and VN [18,23] Moreover, VN is a glycoprotein containing multiple cell receptor binding sites including integrins, uPAR and PAI-1 [24], and which can therefore form transitory ECM element-cell junctions.…”

“…1). The SCAs pertaining to the SK-N-BE(2) cell line in chromosomes7,11,13,19, and 20 were either absent or were only observed in proportionally few cells in tumors from VN-KO mice(Fig 1). Finally, NCA of chromosome 18 turned into a SCA in P1 to P3 including 18pq-(pter-q22.2, 67Mb) with the nal fragment 18q(22.2-ter, 11 Mb) as a CNLOH(Fig.…”

Impact of extracellular matrix properties on neuroblastoma genomic heterogeneity

“…We previously de ned an aggressive pattern of rigid ECMs in high-risk NB (HR-NB) [18]. NB stiff ECM is rich in cross-linked collagen III bers, poor in glycosaminoglycans, supporting sinusoidal vascular structures (blood and lymphatic) and with a high quantity of territorial vitronectin (VN, located in the cytoplasmic compartment and in a thin layer around the tumor cells) [19][20][21][22]. NB stiff ECM is also rich in collagen I bers and bronectin but in less amount and with a more physiological-like topology than collagen III and VN [18,23] Moreover, VN is a glycoprotein containing multiple cell receptor binding sites including integrins, uPAR and PAI-1 [24], and which can therefore form transitory ECM elements-cell junctions.…”