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HSPA12B: a novel facilitator of lung tumor growth.

Ma H, Lu T, Zhang X, Li C, Xiong J, Huang L, Liu P, Li Y, Liu L, Ding Z - Oncotarget (2015)

Bottom Line: Tg tumors exhibited increased angiogenesis and proliferation while reduced apoptosis compared with WT 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.

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.

No MeSH data available.


Related in: MedlinePlus

Endothelial HSPA12B facilitated lung tumor growth(A) Immunoblotting for HSPA12B. Lung tissues from WT and Tg mice (8-week old) were prepared for immunoblotting for HSPA12B. The same membrane was blotted with α-Tubulin to serve as a loading control. *P<0.01, n=6 per group. (B) Immunofluorescence for HSPA12B. Lung tissues from Tg mice (8-week old) were prepared for cryosectioning. The immunofluorescence staining for HSPA12B and PCAM-1 was performed. Note that HSPA12B (FITC) was colocalized with PCAM-1 (Cy3). Representative images from three independent experiments are shown. (C) Tumor formation. WT and Tg mice were implanted with LLCs to induce lung tumorigenesis. Lung tumor formation was examined and photographed 18 days after LLCs implantation. Note that Tg mice had a higher number and bigger size of tumors than WT mice. n=7- 9 per group. (D) Tumor number. WT and Tg mice were implanted with LLCs to induce lung tumorigenesis. Eighteen days later, the tumors were isolated from lungs for tumor number counting. *P<0.01, n=7- 9 per group. (E) Tumor Burden. WT and Tg mice were implanted with LLCs to induce lung tumorigenesis. Eighteen days later, the tumors were isolated from lungs for tumor burden weighing. *P<0.01, n=7- 9 per group. All quantitative data are expressed as means ± SD.
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Figure 1: Endothelial HSPA12B facilitated lung tumor growth(A) Immunoblotting for HSPA12B. Lung tissues from WT and Tg mice (8-week old) were prepared for immunoblotting for HSPA12B. The same membrane was blotted with α-Tubulin to serve as a loading control. *P<0.01, n=6 per group. (B) Immunofluorescence for HSPA12B. Lung tissues from Tg mice (8-week old) were prepared for cryosectioning. The immunofluorescence staining for HSPA12B and PCAM-1 was performed. Note that HSPA12B (FITC) was colocalized with PCAM-1 (Cy3). Representative images from three independent experiments are shown. (C) Tumor formation. WT and Tg mice were implanted with LLCs to induce lung tumorigenesis. Lung tumor formation was examined and photographed 18 days after LLCs implantation. Note that Tg mice had a higher number and bigger size of tumors than WT mice. n=7- 9 per group. (D) Tumor number. WT and Tg mice were implanted with LLCs to induce lung tumorigenesis. Eighteen days later, the tumors were isolated from lungs for tumor number counting. *P<0.01, n=7- 9 per group. (E) Tumor Burden. WT and Tg mice were implanted with LLCs to induce lung tumorigenesis. Eighteen days later, the tumors were isolated from lungs for tumor burden weighing. *P<0.01, n=7- 9 per group. All quantitative data are expressed as means ± SD.

Mentions: To investigate the roles of HSPA12B in lung cancer progression, we generated HSPA12B Tg mice. As shown in Figure 1A, HSPA12B protein levels were significantly higher (212.6%) in Tg lung tissues than in WT controls (P < 0.01). Immunofluorescence staining showed that HSPA12B (green) in Tg lung sections colocalized with PCAM-1 (red), a marker of endothelial cells (Figure 1B). Collectively, the results suggest that HSPA12B was overexpressed in pulmonary endothelial cells in Tg mice.


HSPA12B: a novel facilitator of lung tumor growth.

Ma H, Lu T, Zhang X, Li C, Xiong J, Huang L, Liu P, Li Y, Liu L, Ding Z - Oncotarget (2015)

Endothelial HSPA12B facilitated lung tumor growth(A) Immunoblotting for HSPA12B. Lung tissues from WT and Tg mice (8-week old) were prepared for immunoblotting for HSPA12B. The same membrane was blotted with α-Tubulin to serve as a loading control. *P<0.01, n=6 per group. (B) Immunofluorescence for HSPA12B. Lung tissues from Tg mice (8-week old) were prepared for cryosectioning. The immunofluorescence staining for HSPA12B and PCAM-1 was performed. Note that HSPA12B (FITC) was colocalized with PCAM-1 (Cy3). Representative images from three independent experiments are shown. (C) Tumor formation. WT and Tg mice were implanted with LLCs to induce lung tumorigenesis. Lung tumor formation was examined and photographed 18 days after LLCs implantation. Note that Tg mice had a higher number and bigger size of tumors than WT mice. n=7- 9 per group. (D) Tumor number. WT and Tg mice were implanted with LLCs to induce lung tumorigenesis. Eighteen days later, the tumors were isolated from lungs for tumor number counting. *P<0.01, n=7- 9 per group. (E) Tumor Burden. WT and Tg mice were implanted with LLCs to induce lung tumorigenesis. Eighteen days later, the tumors were isolated from lungs for tumor burden weighing. *P<0.01, n=7- 9 per group. All quantitative data are expressed as means ± SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496407&req=5

Figure 1: Endothelial HSPA12B facilitated lung tumor growth(A) Immunoblotting for HSPA12B. Lung tissues from WT and Tg mice (8-week old) were prepared for immunoblotting for HSPA12B. The same membrane was blotted with α-Tubulin to serve as a loading control. *P<0.01, n=6 per group. (B) Immunofluorescence for HSPA12B. Lung tissues from Tg mice (8-week old) were prepared for cryosectioning. The immunofluorescence staining for HSPA12B and PCAM-1 was performed. Note that HSPA12B (FITC) was colocalized with PCAM-1 (Cy3). Representative images from three independent experiments are shown. (C) Tumor formation. WT and Tg mice were implanted with LLCs to induce lung tumorigenesis. Lung tumor formation was examined and photographed 18 days after LLCs implantation. Note that Tg mice had a higher number and bigger size of tumors than WT mice. n=7- 9 per group. (D) Tumor number. WT and Tg mice were implanted with LLCs to induce lung tumorigenesis. Eighteen days later, the tumors were isolated from lungs for tumor number counting. *P<0.01, n=7- 9 per group. (E) Tumor Burden. WT and Tg mice were implanted with LLCs to induce lung tumorigenesis. Eighteen days later, the tumors were isolated from lungs for tumor burden weighing. *P<0.01, n=7- 9 per group. All quantitative data are expressed as means ± SD.
Mentions: To investigate the roles of HSPA12B in lung cancer progression, we generated HSPA12B Tg mice. As shown in Figure 1A, HSPA12B protein levels were significantly higher (212.6%) in Tg lung tissues than in WT controls (P < 0.01). Immunofluorescence staining showed that HSPA12B (green) in Tg lung sections colocalized with PCAM-1 (red), a marker of endothelial cells (Figure 1B). Collectively, the results suggest that HSPA12B was overexpressed in pulmonary endothelial cells in Tg mice.

Bottom Line: Tg tumors exhibited increased angiogenesis and proliferation while reduced apoptosis compared with WT 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.

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.

No MeSH data available.


Related in: MedlinePlus