Transforming Growth Factor-β1 and -β2 in Gastric Precancer and Cancer and Roles in Tumor-Cell Interactions with Peripheral Blood Mononuclear Cells In Vitro
Transforming growth factor-β1 (TGF-β1) and -β2 are correlated with poorer prognosis in gastric cancer (GC), which act in both tumor and immune cells. However, their expressions in precancer and tumor-cell interactions with peripheral blood mononuclear cells (PBMCs) remain unclear. Protein levels of...
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Public Library of Science
2013
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544811/ |
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pubmed-35448112013-01-22 Transforming Growth Factor-β1 and -β2 in Gastric Precancer and Cancer and Roles in Tumor-Cell Interactions with Peripheral Blood Mononuclear Cells In Vitro Ma, Gui-Fen Miao, Qing Zeng, Xiao-Qing Luo, Tian-Cheng Ma, Li-Li Liu, Yi-Mei Lian, Jing-Jing Gao, Hong Chen, Shi-Yao Research Article Transforming growth factor-β1 (TGF-β1) and -β2 are correlated with poorer prognosis in gastric cancer (GC), which act in both tumor and immune cells. However, their expressions in precancer and tumor-cell interactions with peripheral blood mononuclear cells (PBMCs) remain unclear. Protein levels of TGF-β1 and -β2 were analyzed by immunohistochemistry and corresponding mRNA levels were determined by quantitative real-time polymerase chain reaction in 93 surgical and biopsy specimens. Serum TGF-β concentration was detected by enzyme-linked immunosorbent assays. AGS and MKN45 cell lines were directly or indirectly cocultured with PBMCs in vitro. TGF-β and Smad molecules were detected after cocultures and the growths of GC cells and PBMCs were assessed by cell proliferation assay. The results showed positive staining for TGF-β1 was detected in 20% of control samples, 52.3% of precancer, 59.1% of early GC and 66.7% of advanced GC samples, correlated with lesion progression (χ2 = 9.487, P = 0.002). All tissues were positive for TGF-β2. TGF-β1 mRNA levels were increased in advanced cancers, while TGF-β2 increased earlier. TGF-β1 mRNA levels were higher in tumor than in peritumor, which positively correlated with Smad2 and Smad7. Serum TGF-β levels were significantly higher in patients with early and advanced cancers compared to controls (TGF-β1∶50.08±4.38 and 45.76±5.00 vs. 27.78±6.11 ng/mL; TGF-β2∶133.61±21.90 and 111.34±15.76 vs. 59.41±15.42 ng/mL, both P<0.05). The levels of TGF-β1 mRNA and cytokine secretion were higher in GC cells after direct coculture compared to indirect culture. TGF-β1 was decreased and TGF-β2 was increased in PBMCs after cocultures. Moreover, TGF-β1 inhibited the viability of PBMCs but not cancer cells. Collectively, neoplastic transformation may be an early event involving the increase of TGF-β1 in the general and local environment. TGF-β1 production is promoted by the direct interaction between GC cells and PBMCs, which might facilitate cancer development. Public Library of Science 2013-01-14 /pmc/articles/PMC3544811/ /pubmed/23342108 http://dx.doi.org/10.1371/journal.pone.0054249 Text en © 2013 Ma et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Ma, Gui-Fen Miao, Qing Zeng, Xiao-Qing Luo, Tian-Cheng Ma, Li-Li Liu, Yi-Mei Lian, Jing-Jing Gao, Hong Chen, Shi-Yao |
| spellingShingle |
Ma, Gui-Fen Miao, Qing Zeng, Xiao-Qing Luo, Tian-Cheng Ma, Li-Li Liu, Yi-Mei Lian, Jing-Jing Gao, Hong Chen, Shi-Yao Transforming Growth Factor-β1 and -β2 in Gastric Precancer and Cancer and Roles in Tumor-Cell Interactions with Peripheral Blood Mononuclear Cells In Vitro |
| author_facet |
Ma, Gui-Fen Miao, Qing Zeng, Xiao-Qing Luo, Tian-Cheng Ma, Li-Li Liu, Yi-Mei Lian, Jing-Jing Gao, Hong Chen, Shi-Yao |
| author_sort |
Ma, Gui-Fen |
| title |
Transforming Growth Factor-β1 and -β2 in Gastric Precancer and Cancer and Roles in Tumor-Cell Interactions with Peripheral Blood Mononuclear Cells In Vitro
|
| title_short |
Transforming Growth Factor-β1 and -β2 in Gastric Precancer and Cancer and Roles in Tumor-Cell Interactions with Peripheral Blood Mononuclear Cells In Vitro
|
| title_full |
Transforming Growth Factor-β1 and -β2 in Gastric Precancer and Cancer and Roles in Tumor-Cell Interactions with Peripheral Blood Mononuclear Cells In Vitro
|
| title_fullStr |
Transforming Growth Factor-β1 and -β2 in Gastric Precancer and Cancer and Roles in Tumor-Cell Interactions with Peripheral Blood Mononuclear Cells In Vitro
|
| title_full_unstemmed |
Transforming Growth Factor-β1 and -β2 in Gastric Precancer and Cancer and Roles in Tumor-Cell Interactions with Peripheral Blood Mononuclear Cells In Vitro
|
| title_sort |
transforming growth factor-β1 and -β2 in gastric precancer and cancer and roles in tumor-cell interactions with peripheral blood mononuclear cells in vitro |
| description |
Transforming growth factor-β1 (TGF-β1) and -β2 are correlated with poorer prognosis in gastric cancer (GC), which act in both tumor and immune cells. However, their expressions in precancer and tumor-cell interactions with peripheral blood mononuclear cells (PBMCs) remain unclear. Protein levels of TGF-β1 and -β2 were analyzed by immunohistochemistry and corresponding mRNA levels were determined by quantitative real-time polymerase chain reaction in 93 surgical and biopsy specimens. Serum TGF-β concentration was detected by enzyme-linked immunosorbent assays. AGS and MKN45 cell lines were directly or indirectly cocultured with PBMCs in vitro. TGF-β and Smad molecules were detected after cocultures and the growths of GC cells and PBMCs were assessed by cell proliferation assay. The results showed positive staining for TGF-β1 was detected in 20% of control samples, 52.3% of precancer, 59.1% of early GC and 66.7% of advanced GC samples, correlated with lesion progression (χ2 = 9.487, P = 0.002). All tissues were positive for TGF-β2. TGF-β1 mRNA levels were increased in advanced cancers, while TGF-β2 increased earlier. TGF-β1 mRNA levels were higher in tumor than in peritumor, which positively correlated with Smad2 and Smad7. Serum TGF-β levels were significantly higher in patients with early and advanced cancers compared to controls (TGF-β1∶50.08±4.38 and 45.76±5.00 vs. 27.78±6.11 ng/mL; TGF-β2∶133.61±21.90 and 111.34±15.76 vs. 59.41±15.42 ng/mL, both P<0.05). The levels of TGF-β1 mRNA and cytokine secretion were higher in GC cells after direct coculture compared to indirect culture. TGF-β1 was decreased and TGF-β2 was increased in PBMCs after cocultures. Moreover, TGF-β1 inhibited the viability of PBMCs but not cancer cells. Collectively, neoplastic transformation may be an early event involving the increase of TGF-β1 in the general and local environment. TGF-β1 production is promoted by the direct interaction between GC cells and PBMCs, which might facilitate cancer development. |
| publisher |
Public Library of Science |
| publishDate |
2013 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544811/ |
| _version_ |
1611946933155266560 |