# HSPA12B: a novel facilitator of lung tumor growth

## TL;DR

This study shows that HSPA12B promotes lung tumor growth through a Cox-2-dependent mechanism, suggesting it could be a new target for lung cancer treatment.

## Contribution

The study identifies HSPA12B as a novel facilitator of lung tumor growth and a potential therapeutic target.

## Key findings

- Transgenic mice overexpressing HSPA12B developed more and larger lung tumors compared to wild-type mice.
- HSPA12B-induced tumor growth was suppressed by the Cox-2 inhibitor celecoxib, reducing angiogenesis and proliferation.
- Celecoxib reversed HSPA12B-induced changes in angiopoietin-1, eNOS phosphorylation, and AKAP12 levels.

## 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.