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TMEPAI/PMEPA1 enhances tumorigenic activities in lung cancer cells.

Vo Nguyen TT, Watanabe Y, Shiba A, Noguchi M, Itoh S, Kato M - Cancer Sci. (2014)

Bottom Line: TMEPAI is constitutively and highly expressed in many types of cancer and is associated with poor prognosis.Knockdown of TMEPAI in Calu3 and NCI-H23 cells enhanced levels of Smad2 phosphorylation and significantly suppressed cell proliferation in the presence of TGF-β, indicating that highly expressed TMEPAI suppresses levels of Smad phosphorylation in these cancer cells and reduces the growth inhibitory effects of TGF-β/Smad signaling.Together, these experiments indicate that TMEPAI promotes tumorigenic activities in lung cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

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Related in: MedlinePlus

Calu3-shTMEPAI cells have decreased tumorigenic activity in the lungs. TMEPAI-knockdown Calu3 cells (Calu3-sh#9 and Calu3-sh#10) were injected into the tail vein of NOD-SCID mice (106 cells in 200 μL PBS/mice). (a) After 8 weeks, the lungs were collected and photographed. (b) The thin sections of lungs were stained with H&E. Scale bar = 1 mm. Higher magnifications show a typical metastatic area. (c) The percentages of tumor areas were measured by image analyses. The means ± SDs are shown. *P < 0.01 (vs control). (d) The same lung sections as those in (b) were stained with anti-Ki67 antibodies. The nuclei of proliferating cancer cells showed positive staining. Scale bar = 100 μm. Calu3 sh. control, Calu3 sh. control expresses non-targeting shRNA (SHC002, Sigma) in pLKO.1-puro vector.
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fig06: Calu3-shTMEPAI cells have decreased tumorigenic activity in the lungs. TMEPAI-knockdown Calu3 cells (Calu3-sh#9 and Calu3-sh#10) were injected into the tail vein of NOD-SCID mice (106 cells in 200 μL PBS/mice). (a) After 8 weeks, the lungs were collected and photographed. (b) The thin sections of lungs were stained with H&E. Scale bar = 1 mm. Higher magnifications show a typical metastatic area. (c) The percentages of tumor areas were measured by image analyses. The means ± SDs are shown. *P < 0.01 (vs control). (d) The same lung sections as those in (b) were stained with anti-Ki67 antibodies. The nuclei of proliferating cancer cells showed positive staining. Scale bar = 100 μm. Calu3 sh. control, Calu3 sh. control expresses non-targeting shRNA (SHC002, Sigma) in pLKO.1-puro vector.

Mentions: To examine the effects of TMEPAI on the metastatic potential in lungs, we injected Calu3-sh#9 and Calu3-sh#10 cells into the tail veins of NOD-SCID mice. Eight weeks after injection, mice were killed and the collected lungs were examined histopathologically with H&E staining. We also stained for Ki-67 to detect proliferating cancer cells. Using morphometric software, we calculated the percentage of the representative tumor areas in the total lung areas. Calu3-sh#9 and Calu3-sh#10 cells formed significantly smaller tumors both is size and numbers than those of the control Calu3 cells (Fig.6). These results indicated that knockdown of TMEPAI suppresses the ability of lung cancer cells to develop metastatic tumors in lungs.


TMEPAI/PMEPA1 enhances tumorigenic activities in lung cancer cells.

Vo Nguyen TT, Watanabe Y, Shiba A, Noguchi M, Itoh S, Kato M - Cancer Sci. (2014)

Calu3-shTMEPAI cells have decreased tumorigenic activity in the lungs. TMEPAI-knockdown Calu3 cells (Calu3-sh#9 and Calu3-sh#10) were injected into the tail vein of NOD-SCID mice (106 cells in 200 μL PBS/mice). (a) After 8 weeks, the lungs were collected and photographed. (b) The thin sections of lungs were stained with H&E. Scale bar = 1 mm. Higher magnifications show a typical metastatic area. (c) The percentages of tumor areas were measured by image analyses. The means ± SDs are shown. *P < 0.01 (vs control). (d) The same lung sections as those in (b) were stained with anti-Ki67 antibodies. The nuclei of proliferating cancer cells showed positive staining. Scale bar = 100 μm. Calu3 sh. control, Calu3 sh. control expresses non-targeting shRNA (SHC002, Sigma) in pLKO.1-puro vector.
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fig06: Calu3-shTMEPAI cells have decreased tumorigenic activity in the lungs. TMEPAI-knockdown Calu3 cells (Calu3-sh#9 and Calu3-sh#10) were injected into the tail vein of NOD-SCID mice (106 cells in 200 μL PBS/mice). (a) After 8 weeks, the lungs were collected and photographed. (b) The thin sections of lungs were stained with H&E. Scale bar = 1 mm. Higher magnifications show a typical metastatic area. (c) The percentages of tumor areas were measured by image analyses. The means ± SDs are shown. *P < 0.01 (vs control). (d) The same lung sections as those in (b) were stained with anti-Ki67 antibodies. The nuclei of proliferating cancer cells showed positive staining. Scale bar = 100 μm. Calu3 sh. control, Calu3 sh. control expresses non-targeting shRNA (SHC002, Sigma) in pLKO.1-puro vector.
Mentions: To examine the effects of TMEPAI on the metastatic potential in lungs, we injected Calu3-sh#9 and Calu3-sh#10 cells into the tail veins of NOD-SCID mice. Eight weeks after injection, mice were killed and the collected lungs were examined histopathologically with H&E staining. We also stained for Ki-67 to detect proliferating cancer cells. Using morphometric software, we calculated the percentage of the representative tumor areas in the total lung areas. Calu3-sh#9 and Calu3-sh#10 cells formed significantly smaller tumors both is size and numbers than those of the control Calu3 cells (Fig.6). These results indicated that knockdown of TMEPAI suppresses the ability of lung cancer cells to develop metastatic tumors in lungs.

Bottom Line: TMEPAI is constitutively and highly expressed in many types of cancer and is associated with poor prognosis.Knockdown of TMEPAI in Calu3 and NCI-H23 cells enhanced levels of Smad2 phosphorylation and significantly suppressed cell proliferation in the presence of TGF-β, indicating that highly expressed TMEPAI suppresses levels of Smad phosphorylation in these cancer cells and reduces the growth inhibitory effects of TGF-β/Smad signaling.Together, these experiments indicate that TMEPAI promotes tumorigenic activities in lung cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

Show MeSH
Related in: MedlinePlus