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Increased IL-10 mRNA expression in tumor-associated macrophage correlated with late stage of lung cancer.

Wang R, Lu M, Zhang J, Chen S, Luo X, Qin Y, Chen H - J. Exp. Clin. Cancer Res. (2011)

Bottom Line: We successfully achieved up to 95% purity of TAM, derived from 63 primary lung cancer tissues.Our results revealed that TAM with high levels of IL-10 expression may play an important role in the progression of non-small cell lung cancer.Additionally, the phenotype of isolated TAM can be potentially used to predict clinicopathological features as well.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Thoracic Surgery, Shanghai Cancer Hospital, Fudan University, China.

ABSTRACT

Background: Monocyte recruited into the tumor and maturation to tumor-associated macrophage (TAM). Interleukin-10(IL-10) is a potent immunosuppressive cytokine, which can be secreted from both primary tumor and stromal cells. However, there are controversies regarding its role in the progression of cancer. So it is important to isolate TAM from tumor cells to study the role of IL-10 in the progress of cancer. The aim of our study was to determine whether IL-10 expressed by TAM correlated with clinicopathological factors in NSCLC.

Methods: TAM in NSCLC was isolated by short-term culture in serum free medium with the modification to literature reports. The mRNA expression levels of IL-10, cathepsin B, cathepsin S, which were closely related with TAM according to the literatures, were evaluated by Quantitative real-time RT-PCR in 63 NSCLC. The relationships between their expression levels and clinicopathological features were investigated.

Results: We successfully achieved up to 95% purity of TAM, derived from 63 primary lung cancer tissues. TAM expressed high levels of IL-10, cathepsin B in NSCLC. High levels of IL-10 in TAM significantly correlated with stage, tumor size, lymph node metastasis, lymphovascular invasion or histologic poor differentiation.

Conclusions: Our results revealed that TAM with high levels of IL-10 expression may play an important role in the progression of non-small cell lung cancer. The data also suggested that TAMs may involve in tumor immunosuppression through overexpressed IL-10. Additionally, the phenotype of isolated TAM can be potentially used to predict clinicopathological features as well.

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Immunohistochemical expression of IL-10, cathepsin B and CD68 in macrophage. A-B, High IL-10 expression in macrophage, A, IL-10 staining in macrophage (strong positivity); B, CD68 staining. C-D, Cathepsin B expression in macrophage; C, cathepsin B staining in macrophage (most cells were moderate positivity, only a few cells were strong staining); D, CD68 staining. Scale bar indicates 50 μm. Original magnification, × 400.
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Figure 5: Immunohistochemical expression of IL-10, cathepsin B and CD68 in macrophage. A-B, High IL-10 expression in macrophage, A, IL-10 staining in macrophage (strong positivity); B, CD68 staining. C-D, Cathepsin B expression in macrophage; C, cathepsin B staining in macrophage (most cells were moderate positivity, only a few cells were strong staining); D, CD68 staining. Scale bar indicates 50 μm. Original magnification, × 400.

Mentions: To confirm whether TAMs express IL-10 and cathepsin B in protein level, 6 NSCLC (3 late stage (ⅢA) and 3 early stage (Ia- Ib)) were randomly selected to perform IHC using antibody against CD68, IL-10 and cathepsin B on serial sections. We demonstrated that almost all CD68 positive cells co-expressing IL-10, which in line with the QRT-PCR results that the IL-10 mRNA expression level is high (Figure 5 A-B). The IL-10 expression was negative by IHC in 3 early stage NSCLC, which in line with the QRT-PCR results that the IL-10 mRNA expression level below the median (30.5) in 3 early stage NSCLC. Expression of cathepsin B in macrophage was observed in 5 of 6 cases. Among macrophages expressing cathepsin B, only a small portion of the cells showed strong positive (Figure 5 C-D) and not associated with stage of disease.


Increased IL-10 mRNA expression in tumor-associated macrophage correlated with late stage of lung cancer.

Wang R, Lu M, Zhang J, Chen S, Luo X, Qin Y, Chen H - J. Exp. Clin. Cancer Res. (2011)

Immunohistochemical expression of IL-10, cathepsin B and CD68 in macrophage. A-B, High IL-10 expression in macrophage, A, IL-10 staining in macrophage (strong positivity); B, CD68 staining. C-D, Cathepsin B expression in macrophage; C, cathepsin B staining in macrophage (most cells were moderate positivity, only a few cells were strong staining); D, CD68 staining. Scale bar indicates 50 μm. Original magnification, × 400.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3117740&req=5

Figure 5: Immunohistochemical expression of IL-10, cathepsin B and CD68 in macrophage. A-B, High IL-10 expression in macrophage, A, IL-10 staining in macrophage (strong positivity); B, CD68 staining. C-D, Cathepsin B expression in macrophage; C, cathepsin B staining in macrophage (most cells were moderate positivity, only a few cells were strong staining); D, CD68 staining. Scale bar indicates 50 μm. Original magnification, × 400.
Mentions: To confirm whether TAMs express IL-10 and cathepsin B in protein level, 6 NSCLC (3 late stage (ⅢA) and 3 early stage (Ia- Ib)) were randomly selected to perform IHC using antibody against CD68, IL-10 and cathepsin B on serial sections. We demonstrated that almost all CD68 positive cells co-expressing IL-10, which in line with the QRT-PCR results that the IL-10 mRNA expression level is high (Figure 5 A-B). The IL-10 expression was negative by IHC in 3 early stage NSCLC, which in line with the QRT-PCR results that the IL-10 mRNA expression level below the median (30.5) in 3 early stage NSCLC. Expression of cathepsin B in macrophage was observed in 5 of 6 cases. Among macrophages expressing cathepsin B, only a small portion of the cells showed strong positive (Figure 5 C-D) and not associated with stage of disease.

Bottom Line: We successfully achieved up to 95% purity of TAM, derived from 63 primary lung cancer tissues.Our results revealed that TAM with high levels of IL-10 expression may play an important role in the progression of non-small cell lung cancer.Additionally, the phenotype of isolated TAM can be potentially used to predict clinicopathological features as well.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Thoracic Surgery, Shanghai Cancer Hospital, Fudan University, China.

ABSTRACT

Background: Monocyte recruited into the tumor and maturation to tumor-associated macrophage (TAM). Interleukin-10(IL-10) is a potent immunosuppressive cytokine, which can be secreted from both primary tumor and stromal cells. However, there are controversies regarding its role in the progression of cancer. So it is important to isolate TAM from tumor cells to study the role of IL-10 in the progress of cancer. The aim of our study was to determine whether IL-10 expressed by TAM correlated with clinicopathological factors in NSCLC.

Methods: TAM in NSCLC was isolated by short-term culture in serum free medium with the modification to literature reports. The mRNA expression levels of IL-10, cathepsin B, cathepsin S, which were closely related with TAM according to the literatures, were evaluated by Quantitative real-time RT-PCR in 63 NSCLC. The relationships between their expression levels and clinicopathological features were investigated.

Results: We successfully achieved up to 95% purity of TAM, derived from 63 primary lung cancer tissues. TAM expressed high levels of IL-10, cathepsin B in NSCLC. High levels of IL-10 in TAM significantly correlated with stage, tumor size, lymph node metastasis, lymphovascular invasion or histologic poor differentiation.

Conclusions: Our results revealed that TAM with high levels of IL-10 expression may play an important role in the progression of non-small cell lung cancer. The data also suggested that TAMs may involve in tumor immunosuppression through overexpressed IL-10. Additionally, the phenotype of isolated TAM can be potentially used to predict clinicopathological features as well.

Show MeSH
Related in: MedlinePlus