Validation of COL11A1/procollagen 11A1 expression in TGF-β1-activated immortalised human mesenchymal cells and in stromal cells of human colon adenocarcinoma

Abstract

BackgroundThe human COL11A1 gene has been shown to be up-regulated in stromal cells of colorectal tumours, but, so far, the immunodetection of procollagen 11A1, the primary protein product of COL11A1, has not been studied in detail in human colon adenocarcinomas. Some cancer-associated stromal cells seem to be derived from bone marrow mesenchymal cells; the expression of the COL11A1 gene and the parallel immunodetection of procollagen 11A1 have not been evaluated in these latter cells, either.MethodsWe used quantitative RT-PCR and/or immunocytochemistry to study the expression of DES/desmin, VIM/vimentin, ACTA2/αSMA (alpha smooth muscle actin) and COL11A1/procollagen 11A1 in HCT 116 human colorectal adenocarcinoma cells, in immortalised human bone marrow mesenchymal cells and in human colon adenocarcinoma-derived cultured stromal cells. The immunodetection of procollagen 11A1 was performed with the new recently described DMTX1/1E8.33 mouse monoclonal antibody. Human colon adenocarcinomas and non-malignant colon tissues were evaluated by immunohistochemistry as well. Statistical associations were sought between anti-procollagen 11A1 immunoscoring and patient clinicopathological features.ResultsProcollagen 11A1 was immunodetected in human bone marrow mesenchymal cells and in human colon adenocarcinoma-associated spindle-shaped stromal cells but not in colon epithelial or stromal cells of the normal colon. This immunodetection paralleled, in both kinds of cells, that of the other mesenchymal-related biomarkers studied: vimentin and alpha smooth muscle actin, but not desmin. Thus, procollagen 11A1+ adenocarcinoma-associated stromal cells are similar to “activated myofibroblasts”. In the series of human colon adenocarcinomas here studied, a high procollagen 11A1 expression was associated with nodal involvement (p = 0.05), the development of distant metastases (p = 0.017), and advanced Dukes stages (p = 0.047).ConclusionThe immunodetection of procollagen 11A1 in cancer-associated stromal cells could be a useful biomarker for human colon adenocarcinoma characterisation.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-867) contains supplementary material, which is available to authorized users.

Insight On Colorectal Carcinoma Infiltration by Studying Perilesional Extracellular Matrix

“…Moreover, COL11A1 with a high level of OH-Lys was expressed only in CRC ECM ( Fig. 4E ), in agreement with a report showing COL11A1 to be produced by cancer-associated myofibroblasts and not expressed in the healthy colon 33 .…”

Gene expression profiling of breast cancer in Lebanese women

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Single-cell analysis reveals the pan-cancer invasiveness-associated transition of adipose-derived stromal cells into COL11A1-expressing cancer-associated fibroblasts

“…as they undergo epithelial-to-mesenchymal transition (EMT). It appears that TGF-beta signaling plays an important role in the transformation, as we had speculated by the prominent presence of related genes INHBA and THBS2 (1), and as also proposed by various studies (14,46,47).…”