Oncotarget

Research Papers:

HSPA12B: a novel facilitator of lung tumor growth

He Ma, Ting Lu, Xiaojin Zhang, Chuanfu Li, Jingwei Xiong, Lei Huang, Ping Liu, Yuehua Li, Li Liu and Zhengnian Ding _

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Oncotarget. 2015; 6:9924-9936. https://doi.org/10.18632/oncotarget.3533

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Abstract

He Ma1,*, Ting Lu1,*, Xiaojin Zhang2,*, Chuanfu Li3, Jingwei Xiong1, Lei Huang1, Ping Liu4, Yuehua Li5, Li Liu2 and Zhengnian Ding1

1 Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing, China

2 Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing, China

3 Department of Surgery, East Tennessee State University, Johnson City, TN, USA

4 Department of Oncology, First Affiliated Hospital with Nanjing Medical University, Nanjing, China

5 Department of Pathophysiology, Nanjing Medical University, Nanjing, China

* These authors contributed equally to this work

Correspondence to:

Zhengnian Ding, email:

Li Liu, email:

Keywords: heat shock protein A12B, lung cancer, angiogenesis, proliferation, apoptosis

Received: October 16, 2014 Accepted: February 17, 2015 Published: March 12, 2015

Abstract

Lung tumor progression is regulated by proangiogenic factors. Heat shock protein A12B (HSPA12B) is a recently identified regulator of expression of proangiogenic factors. However, whether HSPA12B plays a role in lung tumor growth is unknown. To address this question, transgenic mice overexpressing HSPA12B (Tg) and wild-type littermates (WT) were implanted with Lewis lung cancer cells to induce lung tumorigenesis. Tg mice showed significantly higher number and bigger size of tumors than WT mice. Tg tumors exhibited increased angiogenesis and proliferation while reduced apoptosis compared with WT tumors. Interestingly, a significantly enhanced upregulation of Cox-2 was detected in Tg tumors than in WT tumors. Also, Tg tumors demonstrated upregulation of VEGF and angiopoietin-1, downregulation of AKAP12, and increased eNOS phosphorylation compared with WT tumors. Celecoxib, a selective Cox-2 inhibitor, suppressed the HSPA12B-induced increase in lung tumor burden. Moreover, celecoxib decreased angiogenesis and proliferation whereas increased apoptosis in Tg tumors. Additionally, celecoxib reduced angiopoietin-1 expression and eNOS phosphorylation but increased AKAP12 levels in Tg tumors. Our results indicate that HSPA12B stimulates lung tumor growth via a Cox-2-dependent mechanism. The present study identified HSPA12B as a novel facilitator of lung tumor growth and a potential therapeutic target for the treatment of lung cancer.


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