Heat shock protein family D member 1 mediates lung cancer cell‑induced angiogenesis of endothelial cells

Keerakarn Somsuan; Artitaya Rongjumnong; Atthapan Morchang; Phateep Hankittichai; Jatuporn Ngoenkam; Anupong Makeudom; Kriengsak Lirdprapamongkol; Suttichai Krisanaprakornkit; Sutatip Pongcharoen; Jisnuson Svasti; Siripat Aluksanasuwan

doi:10.3892/br.2025.1955

Heat shock protein family D member 1 mediates lung cancer cell‑induced angiogenesis of endothelial cells

Biomed Rep. 2025 Feb 27;22(5):77. doi: 10.3892/br.2025.1955. eCollection 2025 May.

Authors

Affiliations

¹ School of Medicine, Mae Fah Luang University, Chiang Rai 57100, Thailand.
² Cancer and Immunology Research Unit, Mae Fah Luang University, Chiang Rai 57100, Thailand.
³ Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand.
⁴ School of Dentistry, Mae Fah Luang University, Chiang Rai 57100, Thailand.
⁵ Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand.
⁶ Department of Medicine, Faculty of Medicine, Naresuan University, Phitsanulok 65000, Thailand.

Abstract

Angiogenesis is a crucial process in lung cancer growth and progression. Heat shock protein family D member 1 (HSPD1 or HSP60) plays a significant role in promoting lung cancer development, but its role in angiogenesis remains largely unexplored. The present study aimed to investigate the involvement of HSPD1 in lung cancer cell-induced angiogenesis using indirect co-culture experiments. Secretomes were collected from stable HSPD1-knockdown A549 lung cancer cells [short hairpin (sh)HSPD1-A549 cells] and scramble control cells (shControl-A549 cells) and used to treat human endothelial EA.hy926 cells. Effects of the secretomes on key steps of angiogenesis, including endothelial cell proliferation, migration, invasion, aggregation and tube formation, were assessed using BrdU incorporation, wound healing, Transwell invasion, hanging-drop and Matrigel tube formation assays, respectively. The amount of vascular endothelial growth factor (VEGF) secreted by EA.hy926 cells was determined using ELISA. The correlation of VEGFA expression with HSPD1 expression and overall survival in patients with lung adenocarcinoma was evaluated using bioinformatics analysis. The results revealed that the shControl-A549 secretome markedly stimulated endothelial cell proliferation, migration, invasion, aggregation, tube formation and VEGF secretion, whereas the shHSPD1-A549 secretome had no significant effects on these processes. VEGFA expression was markedly associated with HSPD1 expression and overall survival in patients with lung adenocarcinoma. In conclusion, the findings highlighted the role of HSPD1 in promoting angiogenesis capability of endothelial cells, potentially through VEGF-mediated pathways. Targeting HSPD1 may represent a promising therapeutic strategy to inhibit angiogenesis and improve clinical outcomes in lung cancer patients.

Keywords: angiogenesis; endothelial cells; heat shock protein family D member 1; lung cancer; vascular endothelial growth factor.