TSP‑1 as a novel biological marker of tumor vasculature normalization in colon carcinoma induced by Endostar

Abstract

Blood vessels in tumors often exhibit abnormal morphology and function, which promotes the growth, metastasis and resistance of tumors to conventional therapies. Therefore, vascular normalization is an emerging strategy to enhance the effectiveness of radiotherapy and chemotherapy when used in combination; however, there is a lack of evidence regarding the optimal schedule for the co-administration of anti-angiogenic and chemotherapeutic drugs. Scheduling treatment is important as the period for normalization is transient, also known as the 'time window'; however, no biomarker has been identified to detect this window. In the present study, recombinant human endostatin (rhES) was employed as an anti-angiogenic agent in xenograft tumor tissue in mice. Following rhES or control (saline) treatment, the density and integrity of tumor vessels were detected by immunofluorescence staining for cluster of differentiation 31 and α-smooth muscle actin; the level of hypoxia in tumor tissue was examined by immunohistochemistry with pimonidazole; the necrotic area was evaluated by hematoxylin and eosin staining; and the level of thrombospondin-1 (TSP-1) in plasma was tested by ELISA. The Cell Counting Kit-8 assay was also used to evaluate the effect of rhES on the proliferation of colon carcinoma SW620 cells. A 'time window' normalized vasculature was determined between day 4 and 6 following rhES treatment, and accompanied by a decrease in hypoxia in tumor tissue. Decreasing plasma TSP-1 levels were consistent with changes in vascular morphology and hypoxia, which exhibited features of normalization. In addition, rhES had no effect on the proliferation of SW620 cells, suggesting that the reduction in TSP-1 was associated with increased oxygen content during vascular normalization, rather than inhibited cell proliferation. In conclusion, TSP-1 may be a potential biomarker for predicting the normalization window of colon cancer vessels.

MicroRNA‑3907 promotes the proliferation and migration of sebaceous gland carcinoma of the eyelid by targeting thrombospondin 1

“…The platelet thrombin protein THBS1, expressed in the cellular membrane, endoplasmic reticulum and extracellular matrix, plays an important role in platelet aggregation, angiogenesis and the occurrence and development of a variety of malignant tumors (32,33). The expression level and roles of THBS1 vary in different tumor types, where it can play either a stimulatory and inhibitory role.…”

Vascular Normalization: A New Window Opened for Cancer Therapies

“…However, on the basis of further research, antitumor efficacy in both types of tumors was increased by combining exercise with chemotherapy, as a result of exercise-induced shear stress activating calcineurin–NFAT–TSP-1 signaling in ECs and promoting tumor vascular normalization in mouse models ( 108 – 111 ). Moreover, the level of TSP-1 had been found in recent studies to be usually elevated around normal vessels compared with abnormal vessels, suggesting that TSP-1 may be a marker of vascular normalization ( 112 ).…”

“…EC proliferation and migration, as well as the expression of VEGF, could be inhibited by an angiogenesis inhibitor, recombinant human endostatin (endostar), which was shown, with recent evidence, to possibly restore vascular homeostasis and induce vascular normalization in some cancer (112,113). However, still unclear is the molecular mechanism, which, in studies, was shown that the Src signaling pathway and matrix metalloproteinase (MMP) might be the mechanism of its action (114,115).…”