Interaction between morphology and angiogenesis in human early colorectal cancers

Okada, Keiichiro; Satoh, Toshimi; Fujimoto, Kazuma; Tokunaga, Osamu

doi:10.1111/j.1440-1827.2004.01650.x

Cited by 8 publications

(6 citation statements)

References 40 publications

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“…The volume of a polypoid lesion is approximately twice that of a nonpolypoid with the same diameter, and the interstitial space available for immune / epithelial cell interaction is thus much larger. Early-stage polypoid colorectal cancers have more extensive microvascular networks than their nonpolypoid counterparts [ 46 ]. A similar difference might exist in precancerous lesions, and this facilitate the immune cells’ infiltration of the stroma of polypoid adenomas.…”

Section: Discussionmentioning

confidence: 99%

The Immune Landscapes of Polypoid and Nonpolypoid Precancerous Colorectal Lesions

Maglietta

Staiano

et al. 2016

PLoS ONE

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Little is known about the immunoediting process in precancerous lesions. We explored this aspect of benign colorectal adenomas with a descriptive analysis of the immune pathways and immune cells whose regulation is linked to the morphology and size of these lesions. Two series of polypoid and nonpolypoid colorectal adenomas were used in this study: 1) 84 samples (42 lesions, each with matched samples of normal mucosa) whose gene expression data were used to quantify the tumor morphology- and size-related dysregulation of immune pathways collected in the Molecular Signature Database, using Gene Set Enrichment Analysis; 2) 40 other lesions examined with immunohistochemistry to quantify the presence of immune cells in the stromal compartment. In the analysis of transcriptomic data, 429 immune pathways displayed significant differential regulation in neoplasms of different morphology and size. Most pathways were significantly upregulated or downregulated in polypoid lesions versus nonpolypoid lesions (regardless of size). Differential pathway regulation associated with lesion size was observed only in polypoid neoplasms. These findings were mirrored by tissue immunostaining with CD4, CD8, FOXP3, MHC-I, CD68, and CD163 antibodies: stromal immune cell counts (mainly T lymphocytes and macrophages) were significantly higher in polypoid lesions. Certain markers displayed significant size-related differences regardless of lesion morphology. Multivariate analysis of variance showed that the marker panel clearly discriminated between precancerous lesions of different morphologies and sizes. Statistical analysis of immunostained cell counts fully support the results of the transcriptomic data analysis: the density of infiltration of most immune cells in the stroma of polypoid precancerous lesions was significantly higher than that observed in nonpolypoid lesions. Large neoplasms also have more immune cells in their stroma than small lesions. Immunoediting in precancerous colorectal tumors may vary with lesion morphology and stage of development, and this variability could influence a given lesion’s trajectory to cancer.

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Section: Discussionmentioning

confidence: 99%

The Immune Landscapes of Polypoid and Nonpolypoid Precancerous Colorectal Lesions

Maglietta

Staiano

et al. 2016

PLoS ONE

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“…4). CD105 is expressed in vascular endothelial cells of polypoid-type early colon cancer [20]. To our knowledge, the present study is the first to identify CD105 expression at levels corresponding to the depth of cancer invasion in the colon adenoma-carcinoma sequence (adenoma, carcinoma in adenoma, adenocarcinoma, and lymph node metastasis).…”

Section: Discussionmentioning

confidence: 99%

“…CD105 is emerging as a prime vascular target of antiangiogenetic cancer therapy [10]. We reported that the predominantly CD105-positive microvessel count of polyploid-type early colon cancer is higher than that of nonpolyploid-type early cancer [20]. However, to our knowledge, the expression of CD105 in vessels of lesions invading all the various tissue layers during the colon adenoma-carcinoma sequence (adenoma, carcinoma in adenoma, and adenocarcinoma) has not been compared with that of other endothelial markers.…”

Section: Introductionmentioning

confidence: 98%

Endoglin (CD105) expression in angiogenesis of colon cancer: analysis using tissue microarrays and comparison with other endothelial markers

et al. 2005

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Some markers of angiogenic endothelial cells are emerging as targets of cancer therapy. The present study compares the expression of CD105 with that of other endothelial markers in all tissue layers during the development of colon cancer. We immunohistochemically analyzed the expression of the colon adenoma-carcinoma sequence by endothelial cells using a panel of eight endothelial markers. We examined sections from endoscopic mucosal resection and surgical resection of tubular adenoma (n=31), carcinoma in adenoma (n=11), and adenocarcinoma (n=34). Cylindrical cores were punched out from donor paraffin blocks of normal mucosa adjacent to tumors, from tumor lesions of mucosa, submucosa, muscularis propria, subserosa, and serosa, and from lymph node metastases. CD31 (PECAM-1) was universally expressed in the blood vessels of adenoma-carcinoma lesions as well as in normal mucosal vessels (80-95%), with no significant differences. In contrast, cancer-associated blood vessels (up to 80%) and cancer cells themselves expressed high levels of CD105. In normal mucosa, CD105 was weakly expressed in endothelial cells of capillaries (< or =21%), and significant differences in its expression in endothelial cells between the normal mucosa and adenoma, carcinoma in adenoma, and adenocarcinoma were found. Flt-1, Flk-1, transforming growth factor-beta1, transforming growth factor-beta receptor II, and CD44 were strongly expressed in the cancer cells but were not expressed in the blood vessels. Vascular endothelial growth factor was expressed at <30% in the blood vessels of adenoma, carcinoma in adenoma, and carcinoma. Moreover, this study provided evidence that CD105 was expressed exclusively in endothelial blood vessels by double immunostaining of CD105 and D2-40. The present study shows that de novo blood vessels of colon cancer specifically express CD105. These findings provide the basis for novel antiangiogenic cancer therapies.

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“…CD105 is predominantly expressed on cellular lineages within the vascular system and is overexpressed on proliferating endothelial cells. Therefore, CD105 is considered to be a powerful marker of neovascularization [24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Active neovascularization and possible vascular-centric development of gastric and periscapular elastofibromas

et al. 2009

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An elastofibroma is a benign and rare fibrous lesion that most commonly occurs in the periscapular region. A gastrointestinal elastofibroma is extremely rare. In the present study, six cases of elastofibromas including a case in the stomach were evaluated. The gastric case revealed widely distributed lesions in the submucosal layer with perivascular fibrotic lesions (PVFLs) and some PVFLs were distributed to the skip lesions of elastofibroma. These PVFLs were also observed in all five periscapular cases and invariably contained elastic fibers which showed various degree of maturation. CD34-positive stromal cells were observed not only in elastofibromas but also in PVFLs in each case. These findings suggested the possibility of the PVFLs were the primary lesions of elastofibroma and their vascular-centric development. The percentage of the CD105-positive vessels in elastofibroma group was significantly higher than in the control group. This result indicates active neovascularization in elastofibromas.

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Interaction between morphology and angiogenesis in human early colorectal cancers

Cited by 8 publications

References 40 publications

The Immune Landscapes of Polypoid and Nonpolypoid Precancerous Colorectal Lesions

The Immune Landscapes of Polypoid and Nonpolypoid Precancerous Colorectal Lesions

Endoglin (CD105) expression in angiogenesis of colon cancer: analysis using tissue microarrays and comparison with other endothelial markers

Active neovascularization and possible vascular-centric development of gastric and periscapular elastofibromas

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