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Tissue transglutaminase mediates the pro-malignant effects of oncostatin M receptor over-expression in cervical squamous cell carcinoma.

Caffarel MM, Chattopadhyay A, Araujo AM, Bauer J, Scarpini CG, Coleman N - J. Pathol. (2013)

Bottom Line: Cervical SCC cells that over-express OSMR show enhanced responsiveness to the major ligand OSM, which induces multiple pro-malignant effects, including increased cell migration and invasiveness.Here, we show that tissue transglutaminase (TGM2) is an important mediator of the ligand-dependent phenotypic effects of OSMR over-expression in SCC cells.We conclude that an OSMR/TGM2/integrin-α5β1/fibronectin pathway is of biological significance in cervical SCC and a candidate for therapeutic targeting.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Cambridge, UK.

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TGM2 expression in cervical and oral SCCs. (A) Linear regression analysis of mRNA levels of TGM2 versus OSMR in microarray expression data for cervical SCC samples (set 1). (B) Correlation between TGM2 protein expression and OSMR copy number in cervical SCC samples (set 2). The left-hand panels show representative images from immunohistochemical staining for TGM2 in cervical SCC samples in which OSMR copy number gain was present (OSMR-G; top row) or absent (OSMR-N; bottom row); scale bars = 100 µm. The right-hand box plot shows the frequency of TGM2-positive SCC cells in samples where OSMR copy number gain was present (OSMR-G) or absent (OSMR-N): bar, median; box, IQR; whiskers, range. (C, D) Expression of TGM2 mRNA in cervical neoplastic progression. TGM2 mRNA expression in normal cervix samples, LSILs, HSILs and SCCs was determined from microarray data derived from sample sets 1 (C) and 3 (D). (E) Expression of TGM2 in oral SCC, based on expression microarray data for sample set 5. The left panel shows levels of TGM2 mRNA in normal oral mucosa and oral SCC tissues, while the right panel shows linear regression analysis of TGM2 mRNA levels versus OSMR mRNA levels in the oral SCC samples
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fig01: TGM2 expression in cervical and oral SCCs. (A) Linear regression analysis of mRNA levels of TGM2 versus OSMR in microarray expression data for cervical SCC samples (set 1). (B) Correlation between TGM2 protein expression and OSMR copy number in cervical SCC samples (set 2). The left-hand panels show representative images from immunohistochemical staining for TGM2 in cervical SCC samples in which OSMR copy number gain was present (OSMR-G; top row) or absent (OSMR-N; bottom row); scale bars = 100 µm. The right-hand box plot shows the frequency of TGM2-positive SCC cells in samples where OSMR copy number gain was present (OSMR-G) or absent (OSMR-N): bar, median; box, IQR; whiskers, range. (C, D) Expression of TGM2 mRNA in cervical neoplastic progression. TGM2 mRNA expression in normal cervix samples, LSILs, HSILs and SCCs was determined from microarray data derived from sample sets 1 (C) and 3 (D). (E) Expression of TGM2 in oral SCC, based on expression microarray data for sample set 5. The left panel shows levels of TGM2 mRNA in normal oral mucosa and oral SCC tissues, while the right panel shows linear regression analysis of TGM2 mRNA levels versus OSMR mRNA levels in the oral SCC samples

Mentions: In our previous study of sample set 1, TGM2 was significantly up-regulated in cervical SCC samples with OSMR over-expression, compared with those that lacked OSMR over-expression 6. There was no association between OSMR and TGM2 gene copy number in this sample set, as assessed by comparative genomic hybridization (data not shown). Using linear regression analysis, we found that levels of TGM2 mRNA correlated significantly with those of OSMR in all the set 1 SCC samples (n = 29; Figure 1A). The frequency of TGM2-positive cells, as determined by immunohistochemistry, was also significantly higher in sections of the 19 cervical SCC samples from set 2 that showed OSMR copy number gain, versus the 18 samples that lacked OSMR copy number gain (Figure 1B).


Tissue transglutaminase mediates the pro-malignant effects of oncostatin M receptor over-expression in cervical squamous cell carcinoma.

Caffarel MM, Chattopadhyay A, Araujo AM, Bauer J, Scarpini CG, Coleman N - J. Pathol. (2013)

TGM2 expression in cervical and oral SCCs. (A) Linear regression analysis of mRNA levels of TGM2 versus OSMR in microarray expression data for cervical SCC samples (set 1). (B) Correlation between TGM2 protein expression and OSMR copy number in cervical SCC samples (set 2). The left-hand panels show representative images from immunohistochemical staining for TGM2 in cervical SCC samples in which OSMR copy number gain was present (OSMR-G; top row) or absent (OSMR-N; bottom row); scale bars = 100 µm. The right-hand box plot shows the frequency of TGM2-positive SCC cells in samples where OSMR copy number gain was present (OSMR-G) or absent (OSMR-N): bar, median; box, IQR; whiskers, range. (C, D) Expression of TGM2 mRNA in cervical neoplastic progression. TGM2 mRNA expression in normal cervix samples, LSILs, HSILs and SCCs was determined from microarray data derived from sample sets 1 (C) and 3 (D). (E) Expression of TGM2 in oral SCC, based on expression microarray data for sample set 5. The left panel shows levels of TGM2 mRNA in normal oral mucosa and oral SCC tissues, while the right panel shows linear regression analysis of TGM2 mRNA levels versus OSMR mRNA levels in the oral SCC samples
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4288975&req=5

fig01: TGM2 expression in cervical and oral SCCs. (A) Linear regression analysis of mRNA levels of TGM2 versus OSMR in microarray expression data for cervical SCC samples (set 1). (B) Correlation between TGM2 protein expression and OSMR copy number in cervical SCC samples (set 2). The left-hand panels show representative images from immunohistochemical staining for TGM2 in cervical SCC samples in which OSMR copy number gain was present (OSMR-G; top row) or absent (OSMR-N; bottom row); scale bars = 100 µm. The right-hand box plot shows the frequency of TGM2-positive SCC cells in samples where OSMR copy number gain was present (OSMR-G) or absent (OSMR-N): bar, median; box, IQR; whiskers, range. (C, D) Expression of TGM2 mRNA in cervical neoplastic progression. TGM2 mRNA expression in normal cervix samples, LSILs, HSILs and SCCs was determined from microarray data derived from sample sets 1 (C) and 3 (D). (E) Expression of TGM2 in oral SCC, based on expression microarray data for sample set 5. The left panel shows levels of TGM2 mRNA in normal oral mucosa and oral SCC tissues, while the right panel shows linear regression analysis of TGM2 mRNA levels versus OSMR mRNA levels in the oral SCC samples
Mentions: In our previous study of sample set 1, TGM2 was significantly up-regulated in cervical SCC samples with OSMR over-expression, compared with those that lacked OSMR over-expression 6. There was no association between OSMR and TGM2 gene copy number in this sample set, as assessed by comparative genomic hybridization (data not shown). Using linear regression analysis, we found that levels of TGM2 mRNA correlated significantly with those of OSMR in all the set 1 SCC samples (n = 29; Figure 1A). The frequency of TGM2-positive cells, as determined by immunohistochemistry, was also significantly higher in sections of the 19 cervical SCC samples from set 2 that showed OSMR copy number gain, versus the 18 samples that lacked OSMR copy number gain (Figure 1B).

Bottom Line: Cervical SCC cells that over-express OSMR show enhanced responsiveness to the major ligand OSM, which induces multiple pro-malignant effects, including increased cell migration and invasiveness.Here, we show that tissue transglutaminase (TGM2) is an important mediator of the ligand-dependent phenotypic effects of OSMR over-expression in SCC cells.We conclude that an OSMR/TGM2/integrin-α5β1/fibronectin pathway is of biological significance in cervical SCC and a candidate for therapeutic targeting.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Cambridge, UK.

Show MeSH
Related in: MedlinePlus