Effects of overexpression of tyrosine kinase receptor 1 on malignant biological behavior of tumor-associated endothelial cells in cervical cancer cells

Acta Universitatis Medicinalis Anhui 2022 11 v.57 1756-1762     font:big middle small

Found programs:

Authors:Sun Qianyu; Wei Yan; Bai Rui; Yang Ping

Keywords:tyrosine kinase receptor 1;tumor-related endothelial cells;cervical cancer;angiogenesis;co-culture

DOI:10.19405/j.cnki.issn1000-1492.2022.11.013

〔Abstract〕 Objective To investigate the effect of overexpression of tyrosine kinase receptor 1(Tie-1) in cervical cancer cells on the malignant biological behavior of tumor-related endothelial cells(TRECs). Methods Immunohistochemical method was used to detect the expression of Tie-1 in cervical cancer cells(CCCs) and TRECs of 96 patients with cervical cancer, and to analyze the correlation between the expression of Tie-1 in TRECs and clinicopathological features and prognosis of patients. HeLa cells overexpressing Tie-1(Hela-Tie1 OE) were constructed, and HeLa-Tie1 OE was co-cultured with human umbilical vein endothelial cells(HUVECs) by Transwell cell co-culture method to obtain cervical cancer TRECs. Western blot was used to analyze Tie-1 protein expression. The migration, invasion and tubulogenesis of TRECs were detected by cell scratch assay, Transwell invasion and migration assay and tubulogenesis assay. Results The expression of Tie-1 was positively correlated with CCCs and TRECs in 96 cervical cancer patients. The positive expression rate of Tie-1 in TRECs of patients with stage(FIGO) ⅠB2-ⅡA, tumor diameter ≥4 cm, cervical muscle invasion depth ≥1/2 full layer, adenocarcinoma, medium and low differentiation cervical cancer was higher than that of patients with ⅠA 1-ⅠB 1, tumor diameter<4 cm, cervical muscle invasion depth<1/2 full layer, squamous carcinoma, and high differentiation cervical cancer, respectively. The differences were statistically significant(P<0.05). The expression of Tie-1 in TRECs of cervical cancer patients had no significant correlation with age, lymph node metastasis and lymphatic space invasion. The positive expression of Tie-1 in cervical cancer TRECs was negatively correlated with 5-year progression-free survival time and overall survival time(P<0.05). The Tie-1 expression of TRECs obtained by co-culture of Hela-Tie1 OE and HUVECs was up-regulated, and the invasion, migration and tubulogenesis of TRECs cells were enhanced. Conclusion The high expression of Tie-1 in TRECs of cervical cancer is related to FIGO stage, tumor diameter, degree of differentiation, depth of cervical muscular invasion, type of cervical cancer, and poor prognosis of patients. Overexpression of Tie-1 can promote TRECs invasion, migration and tubulogenesis.