title: HSPA12B: a novel facilitator of lung tumor growth.
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.
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: He
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Lu
authors.affiliation: Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Surgery, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Oncology, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Nanjing Medical University, Nanjing, China.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Zhengnian
authors.initials: Z
authors.lastname: Ding
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
chemical_list: D018840:HSP70 Heat-Shock Proteins; C472131:HSPA12B protein, human; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: angiogenesis; apoptosis; heat shock protein A12B; lung cancer; proliferation