Background Peroxisome proliferator activated receptor γ （PPARγ） is a ligand-activated transcription factor. Activation of PPARγ has recently been demonstrated to inhibit various tumor cells growth, progression an...Background Peroxisome proliferator activated receptor γ （PPARγ） is a ligand-activated transcription factor. Activation of PPARγ has recently been demonstrated to inhibit various tumor cells growth, progression and metastasis. E-cadherin-mediated cell adhesion system is now considered to be an “invasion suppressor system” in cancer tissues. Matrix metalloproteinases-2 （MMP-2） is a prerequisite for metastasizing tumor cells. However their correlation is still unknown in gastric carcinoma. The aim of this study was to assess the expression of PPAR7, E-cadherin, MMP-2 and their correlation in gastric carcinoma and metastases. Methods Gastric carcinoma tissues and their corresponding lymph nodes with metastases and the adjacent non-tumor tissues were obtained from 54 patients with gastric cancer who underwent gastrectomy. Expression of PPARγ, E-cadherin and MMP-2 was assessed by immunohistochemical staining. Results The nuclear expression level of PPARγ in neoplastic cells was significantly lower than that in the normal controls （P〈0.001）, with the expression of PPARγ being weaker in primary tumors compared with that in metastases. In all neoplastic cells, E-cadherin was expressed with abnormal patterns （cytoplasm pattern, cytoplasm and membrane pattern or absent）, compared with normal cells where E-cadherin was expressed with a normal pattern （membrane pattern）. Compared with the normal tissues, the expression level of E-cadherin decreased in primary tumors and further decreased in metastases （P〈0.001）. Membrane staining of MMP-2 was detected in the foveolar epithelia of normal gastric mucosa, whereas predominant cytoplasm staining of MMP-2 was found in malignant tissues. The expression of MMP-2 was stronger in metastatic tissues than in primary tumors. In neoplastic foci the expression of PPARγ was negatively correlated with MMP-2 expression （P〈0.05）. However, there was no correlation between E-cadherin and PPARγ or MM P-2 expression. Conclusions Down-regulation of PPARγ and E-cadherin and up-regulation of MMP-2 in neoplastic foci might be helpful to gastric carcinogenesis and metastases. An inverse relationship between PPARγ and MMP-2 in human gastric carcinoma suggests that PPARγ might modulate MMP-2 expression and affect gastric cancer metastases.展开更多
基金the grants from the National Natural Science Foundation of China (No. 30671904 and No. 30670949)the Doctor Subjects Foundation of the Ministry of Education of the People's Republic of China (No. 20060558010).
文摘Background Peroxisome proliferator activated receptor γ （PPARγ） is a ligand-activated transcription factor. Activation of PPARγ has recently been demonstrated to inhibit various tumor cells growth, progression and metastasis. E-cadherin-mediated cell adhesion system is now considered to be an “invasion suppressor system” in cancer tissues. Matrix metalloproteinases-2 （MMP-2） is a prerequisite for metastasizing tumor cells. However their correlation is still unknown in gastric carcinoma. The aim of this study was to assess the expression of PPAR7, E-cadherin, MMP-2 and their correlation in gastric carcinoma and metastases. Methods Gastric carcinoma tissues and their corresponding lymph nodes with metastases and the adjacent non-tumor tissues were obtained from 54 patients with gastric cancer who underwent gastrectomy. Expression of PPARγ, E-cadherin and MMP-2 was assessed by immunohistochemical staining. Results The nuclear expression level of PPARγ in neoplastic cells was significantly lower than that in the normal controls （P〈0.001）, with the expression of PPARγ being weaker in primary tumors compared with that in metastases. In all neoplastic cells, E-cadherin was expressed with abnormal patterns （cytoplasm pattern, cytoplasm and membrane pattern or absent）, compared with normal cells where E-cadherin was expressed with a normal pattern （membrane pattern）. Compared with the normal tissues, the expression level of E-cadherin decreased in primary tumors and further decreased in metastases （P〈0.001）. Membrane staining of MMP-2 was detected in the foveolar epithelia of normal gastric mucosa, whereas predominant cytoplasm staining of MMP-2 was found in malignant tissues. The expression of MMP-2 was stronger in metastatic tissues than in primary tumors. In neoplastic foci the expression of PPARγ was negatively correlated with MMP-2 expression （P〈0.05）. However, there was no correlation between E-cadherin and PPARγ or MM P-2 expression. Conclusions Down-regulation of PPARγ and E-cadherin and up-regulation of MMP-2 in neoplastic foci might be helpful to gastric carcinogenesis and metastases. An inverse relationship between PPARγ and MMP-2 in human gastric carcinoma suggests that PPARγ might modulate MMP-2 expression and affect gastric cancer metastases.
