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Involvement of adiponectin in early stage of colorectal carcinogenesis.

Tae CH, Kim SE, Jung SA, Joo YH, Shim KN, Jung HK, Kim TH, Cho MS, Kim KH, Kim JS - BMC Cancer (2014)

Bottom Line: Although altered levels of adiponectin have been reported as a potential risk factor in colorectal cancer (CRC), the importance of the role played by adiponectin in colorectal carcinogenesis has not been established.AdipoRs expression was strong in normal epithelium, but weak to negative in the epithelia of CRC tissues.These findings offer new insight into understanding the relationship between adiponectin and colorectal carcinogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Ewha Medical Research Institute, Ewha Womans University School of Medicine, Seoul, Korea. kimse@ewha.ac.kr.

ABSTRACT

Background: Although altered levels of adiponectin have been reported as a potential risk factor in colorectal cancer (CRC), the importance of the role played by adiponectin in colorectal carcinogenesis has not been established. We sought to examine the expression pattern of adiponectin and adiponectin receptors (AdipoRs) in the normal-adenoma-carcinoma sequence and to assess the implications of adiponectin in colorectal carcinogenesis.

Methods: Serum adiponectin concentrations, and the mRNA and protein expression of adiponectin and AdipoRs were examined using serum and tissues from patients with CRC, advanced adenoma, and a normal colon. mRNA expression of AdipoRs and epithelial-mesenchymal transition regulators including E-cadherin, cyclooxygenase-2 (COX-2) and T-cadherin were examined in HCT116 cells treated with adiponectin.

Results: Serum adiponectin concentrations in patients with advanced adenoma and CRC were lower than those in controls. Adiponectin mRNA was not detected in colonic tissue, whereas AdipoRs mRNA was lower in advanced adenoma and CRC than that in normal colon tissues. Immunohistochemical staining demonstrated that adiponectin was expressed in spindle-shaped cells of the subepithelial layer in normal colon tissues, whereas ill-defined overexpression of adiponectin was seen in the stroma of advanced adenoma and CRC tissues. AdipoRs expression was strong in normal epithelium, but weak to negative in the epithelia of CRC tissues. Adiponectin downregulated COX-2 mRNA expression in vitro, but upregulated T-cadherin in HCT116 cells.

Conclusions: Systemic adiponectin and local AdipoRs expression in the colon may be associated with anti-tumorigenesis during the early stages of CRC. These findings offer new insight into understanding the relationship between adiponectin and colorectal carcinogenesis.

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Immunohistochemical staining of adiponectin, AdipoR1, and AdipoR2. (a–c) Localization of adiponectin staining in normal colon tissue (a, ×200), advanced adenoma (b, ×200) and CRC (c, ×200) differed from spindle-shaped cells in the subepithelial area to a diffuse area in the lamina propria. (d–i) Staining for AdipoR1 (d, ×200) and AdipoR2 (g, ×200) was positive in the epithelium of normal colon tissues. AdipoR1 (e, ×400) and AdipoR2 (h, ×100) showed moderate staining intensities in the epithelial layer of advanced adenoma. In CRC, AdipoR1 (f, ×400) and AdipoR2 (i, ×100) showed weak or no staining.
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Fig3: Immunohistochemical staining of adiponectin, AdipoR1, and AdipoR2. (a–c) Localization of adiponectin staining in normal colon tissue (a, ×200), advanced adenoma (b, ×200) and CRC (c, ×200) differed from spindle-shaped cells in the subepithelial area to a diffuse area in the lamina propria. (d–i) Staining for AdipoR1 (d, ×200) and AdipoR2 (g, ×200) was positive in the epithelium of normal colon tissues. AdipoR1 (e, ×400) and AdipoR2 (h, ×100) showed moderate staining intensities in the epithelial layer of advanced adenoma. In CRC, AdipoR1 (f, ×400) and AdipoR2 (i, ×100) showed weak or no staining.

Mentions: Immunohistochemical staining for adiponectin was performed to compare the adiponectin expression patterns among normal colon, advanced adenoma, and CRC tissues. Adiponectin expression in normal colon tissues was predominantly positive in the subepithelial mesenchymal cells of the lamina propria but not in the colonic epithelial cells. The expression had an appearance similar to the spindle-shaped cells that run parallel to the lining of the epithelium (Figure 3a). However, the adiponectin expression pattern of the thin layer in the subepithelial area was obliterated, while an indeterminate over-expression pattern in stroma was seen in 71.4% of advanced adenoma and 97.4% of CRC tissues (Figure 3b, c).Figure 2


Involvement of adiponectin in early stage of colorectal carcinogenesis.

Tae CH, Kim SE, Jung SA, Joo YH, Shim KN, Jung HK, Kim TH, Cho MS, Kim KH, Kim JS - BMC Cancer (2014)

Immunohistochemical staining of adiponectin, AdipoR1, and AdipoR2. (a–c) Localization of adiponectin staining in normal colon tissue (a, ×200), advanced adenoma (b, ×200) and CRC (c, ×200) differed from spindle-shaped cells in the subepithelial area to a diffuse area in the lamina propria. (d–i) Staining for AdipoR1 (d, ×200) and AdipoR2 (g, ×200) was positive in the epithelium of normal colon tissues. AdipoR1 (e, ×400) and AdipoR2 (h, ×100) showed moderate staining intensities in the epithelial layer of advanced adenoma. In CRC, AdipoR1 (f, ×400) and AdipoR2 (i, ×100) showed weak or no staining.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4232655&req=5

Fig3: Immunohistochemical staining of adiponectin, AdipoR1, and AdipoR2. (a–c) Localization of adiponectin staining in normal colon tissue (a, ×200), advanced adenoma (b, ×200) and CRC (c, ×200) differed from spindle-shaped cells in the subepithelial area to a diffuse area in the lamina propria. (d–i) Staining for AdipoR1 (d, ×200) and AdipoR2 (g, ×200) was positive in the epithelium of normal colon tissues. AdipoR1 (e, ×400) and AdipoR2 (h, ×100) showed moderate staining intensities in the epithelial layer of advanced adenoma. In CRC, AdipoR1 (f, ×400) and AdipoR2 (i, ×100) showed weak or no staining.
Mentions: Immunohistochemical staining for adiponectin was performed to compare the adiponectin expression patterns among normal colon, advanced adenoma, and CRC tissues. Adiponectin expression in normal colon tissues was predominantly positive in the subepithelial mesenchymal cells of the lamina propria but not in the colonic epithelial cells. The expression had an appearance similar to the spindle-shaped cells that run parallel to the lining of the epithelium (Figure 3a). However, the adiponectin expression pattern of the thin layer in the subepithelial area was obliterated, while an indeterminate over-expression pattern in stroma was seen in 71.4% of advanced adenoma and 97.4% of CRC tissues (Figure 3b, c).Figure 2

Bottom Line: Although altered levels of adiponectin have been reported as a potential risk factor in colorectal cancer (CRC), the importance of the role played by adiponectin in colorectal carcinogenesis has not been established.AdipoRs expression was strong in normal epithelium, but weak to negative in the epithelia of CRC tissues.These findings offer new insight into understanding the relationship between adiponectin and colorectal carcinogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Ewha Medical Research Institute, Ewha Womans University School of Medicine, Seoul, Korea. kimse@ewha.ac.kr.

ABSTRACT

Background: Although altered levels of adiponectin have been reported as a potential risk factor in colorectal cancer (CRC), the importance of the role played by adiponectin in colorectal carcinogenesis has not been established. We sought to examine the expression pattern of adiponectin and adiponectin receptors (AdipoRs) in the normal-adenoma-carcinoma sequence and to assess the implications of adiponectin in colorectal carcinogenesis.

Methods: Serum adiponectin concentrations, and the mRNA and protein expression of adiponectin and AdipoRs were examined using serum and tissues from patients with CRC, advanced adenoma, and a normal colon. mRNA expression of AdipoRs and epithelial-mesenchymal transition regulators including E-cadherin, cyclooxygenase-2 (COX-2) and T-cadherin were examined in HCT116 cells treated with adiponectin.

Results: Serum adiponectin concentrations in patients with advanced adenoma and CRC were lower than those in controls. Adiponectin mRNA was not detected in colonic tissue, whereas AdipoRs mRNA was lower in advanced adenoma and CRC than that in normal colon tissues. Immunohistochemical staining demonstrated that adiponectin was expressed in spindle-shaped cells of the subepithelial layer in normal colon tissues, whereas ill-defined overexpression of adiponectin was seen in the stroma of advanced adenoma and CRC tissues. AdipoRs expression was strong in normal epithelium, but weak to negative in the epithelia of CRC tissues. Adiponectin downregulated COX-2 mRNA expression in vitro, but upregulated T-cadherin in HCT116 cells.

Conclusions: Systemic adiponectin and local AdipoRs expression in the colon may be associated with anti-tumorigenesis during the early stages of CRC. These findings offer new insight into understanding the relationship between adiponectin and colorectal carcinogenesis.

Show MeSH
Related in: MedlinePlus