Progressive cellular response in the lamina propria of the colorectal adenoma–carcinoma sequence

Cui, Guanglin; Yuan, Ang; Vonen, Barthold; Florholmen, Jon

doi:10.1111/j.1365-2559.2009.03273.x

Cited by 36 publications

(29 citation statements)

References 45 publications

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“…These cells in the tumor stroma may function as a double-edged sword because they play an important role in both the anticancer response [39,40] and in favoring cancer progression in some certain conditions [26,41,42]. By both the quantitative and qualitative techniques, IDO has been found to be expressed by many types of cells in the tumor microenvironment including tumor cells, fibroblasts, endothelial cells (microvessels), dendritic cells, and macrophages in various cancers [12,20,43,44].…”

Section: Discussionmentioning

confidence: 99%

“…DIHC further confirmed that those IDO-positive surrounding noncancerous cells (brown in g, h, i) were myofibroblasts (red color, labeled by SMA-alpha in g), macrophages (red color, labeled by CD68 in h), and dendritic cells (red color, labeled by S100 in i , and IDO/S100 (to label dendritic cells; monoclonal anti-SMA-alpha, anti-CD68, and anti-S100 antibodies were all purchased from Dako, Carpinteria, CA, USA) according to the manufacturer's instructions and the method described in our publications [25,26]. In brief, the slides were incubated for 30 min with anti-IDO antibody after antigen retrieval and then incubated with labeled polymer-horseradish peroxidase-antimouse and antirabbit antibodies for 10 min at room temperature.…”

Section: Tissue Specimens From Esccs and Controlsmentioning

confidence: 99%

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Localization of indoleamine 2,3-dioxygenase in human esophageal squamous cell carcinomas

Liu

Fuai

et al. 2009

Virchows Arch

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Immunosuppressive factors derived from the tumor and nontumor cells present in the tumor microenvironment contribute to tumor escape from host immune attack. Recently, the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) derived from both the tumor cells and surrounding nontumor cells was found to function as a critical immunosuppressive factor. While the expression of IDO is intensively under investigation in many types of cancers, little information is available in esophageal squamous cell carcinomas (ESCC) thus far. In this study, we have therefore investigated the cellular localization of IDO in 45 ESSCs and ten morphologically normal esophageal tissues; the correlation of IDO with clinicopathological parameters was also analyzed. Immunohistochemistry (IHC) analysis revealed that the density of IDO-positive cells was increased in ESCCs relative to controls (P < 0.01). These cells were distributed as clusters and formed a patchy pattern in both the cancerous epithelium and the surrounding noncancerous cells. Double IHC further confirmed that many IDO-positive cells in the tumor stroma were smooth-muscle-actin-alpha-positive myofibroblasts, CD68-positive macrophages, and S100-positive dendritic cells. Statistical analysis showed that the densities of IDO-positive cells were not significantly correlated with tumor clinical parameters (tumor invasion depth, node metastasis, and TNM stages) and lymphocytic infiltration. Our current findings suggested that the increased IDO expression in ESCCs is from a mixed cellular source (both cancer cells and noncancerous cells). Further studies on immune cell functional analysis are required in the future.

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Section: Discussionmentioning

confidence: 99%

Section: Tissue Specimens From Esccs and Controlsmentioning

confidence: 99%

Localization of indoleamine 2,3-dioxygenase in human esophageal squamous cell carcinomas

Liu

Fuai

et al. 2009

Virchows Arch

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“…IHCs for IL-6 and NF- κ B were performed with Vectastain Elite ABC Kit (Vector Laboratories Inc., Burlingame, CA, USA) according to the manufacturer's instructions and our published method [24]. The following primary antibodies were used: rabbit anti-IL-6 polyclonal antibody (working dilution 1 : 100, Santa Cruz Biotechnology Inc., Santa Cruz, CA, USA) and rabbit anti-NF- κ B polyclonal antibody (working dilution 1 : 100, Santa Cruz Biotechnology Inc., Santa Cruz, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Involvement of NF-κB/IL-6 Pathway in the Processing of Colorectal Carcinogenesis in Colitis Mice

Yang

Ren

et al. 2014

International Journal of Inflammation

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Nuclear factor-kappaB (NF-κB)/interleukin (IL-6) pathway links chronic inflammation to colitis associated cancer (CAC). In this study, we examined the dynamic temporal changes of the NF-κB/IL-6 pathway during the procession of experimental CAC mouse model. Mice were sacrificed after induction for 14, 16, 18, and 22 weeks for the examination of tumor burden, inflammation degree, and protein level of NF-κB and IL-6 in bowel tissues. The results showed that tumor burden and inflammation severity in the bowels were gradually increased over the observed time-points. The expressions of IL-6 and NF-κB proteins were gradually increased after induction of dysplastic lesions over times. These data provide new information on the dynamic temporal changes of NF-κB/IL-6 pathway in relation to CAC development that may be relevant in the design of future investigations of therapeutic interventions to effectively target CAC processes.

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“…Similarly, we have demonstrated that the SMA-α-positive myofibroblast was with a high proliferation capacity in the ESCC tumor stroma and together with the increased infiltration of lymphocyte and macrophage in the same field. A growing body of evidence suggests that fibroblast/myofibroblast activation is a critical factor in promoting cancer invasion and growth [27,31]. In addition, myofibroblast in the tumor stroma is also one of the main cellular sources for COX-2 [29], whereas COX-2 has been demonstrated to be a potential growth factor for cancer cells and a strong stimulator for angiogenesis [13].…”

Section: Discussionmentioning

confidence: 99%

“…To examine the proliferative capacity of different types of tumor stromal cells, double IHCs with proliferating cell nuclear antigen (PCNA)/CD3, PCNA/CD68, and PCNA/ SMA-alpha antibodies (rabbit anti-PCNA antibody was purchased from Santa Cruz Inc, Santa Cruz, CA, USA) were done with EnVision Doublestain System kit (DAKO, Carpinteria, CA, USA) according to the manufacturer's instructions and our published method [27]. The enzyme substrate 3, 3′-diaminobenzidine tetrachloride (DAB) was used for the visualization of anti-PCNA immunoreactivity and Fast Red for the visualization of anti-CD3, anti-CD68, and anti-SMA-alpha immunoreactivities.…”

Section: Double Immunohistochemical Identification Of Proliferation Amentioning

confidence: 99%

Cellular changes in the tumor microenvironment of human esophageal squamous cell carcinomas

Liu

Cui

et al. 2011

Tumor Biol.

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The growth, invasiveness, and metastasis of human cancers are not only determined by the cancer cells but also by their microenvironment. The purpose of this study was to extend our previous studies and to examine the cellular changes in tumor microenvironment (stroma) of esophageal squamous cell carcinomas (ESCCs). The proliferative activity, cellular components, and angiogenesis status in different compartments (non-tumor stroma, tumor stroma, and tumor periphery stroma) of ESCCs were evaluated by immunohistochemistry. The results revealed a hyperproliferative rate labeled by Ki-67 in stromal cells in tumor area as compared with that in stromal cells in non-tumor area, which resulted in the increased densities of myofibroblasts (labeled by smooth muscle actin (SMA)-alpha), lymphocytes (labeled by CD3), macrophages (labeled by CD68), and the activation of angiogenesis characterized by increased microvessel density (MVD) and the increased expression of the proangiogenic factors (vascular endothelial growth factor and interleukin 8) in the tumor stroma. Further analysis showed that the changes of stromal cell density were more significant in the area of periphery tumor stroma than that of stroma between tumor nests. Most cellular changes were significantly associated with lymph node involvement. Double immunohistochemistries with PCNA/CD3, PCNA/CD68, and PCNA/SMA-alpha revealed that these cells present in the ESCC tumor stroma had a proliferative capacity. The cells present in the tumor microenvironment of ESCCs were greatly activated, suggesting that microenvironmental components may be involved in the cancer growth and progression.

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Progressive cellular response in the lamina propria of the colorectal adenoma–carcinoma sequence

Abstract: Progressive cellular responses in the lamina propria could be involved in the adenoma-carcinoma transition.

Cited by 36 publications

References 45 publications

Localization of indoleamine 2,3-dioxygenase in human esophageal squamous cell carcinomas

Localization of indoleamine 2,3-dioxygenase in human esophageal squamous cell carcinomas

Involvement of NF-κB/IL-6 Pathway in the Processing of Colorectal Carcinogenesis in Colitis Mice

Cellular changes in the tumor microenvironment of human esophageal squamous cell carcinomas

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