Age and cellular context influence rectal prolapse formation in mice with caecal wall colorectal cancer xenografts

Tommelein, Joke; Gremonprez, Félix; Verset, Laurine; Vlieghere, Elly De; Wagemans, Glenn; Gespach, Christian; Boterberg, Tom; Demetter, Pieter; Ceelen, Wim; Bracke, Marc; Wever, Olivier De

doi:10.18632/oncotarget.12312

Cited by 5 publications

(6 citation statements)

References 48 publications

(56 reference statements)

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“…COLO320 DM cells are undifferentiated tumorigenic cells that exhibit epithelial to mesenchymal transition (EMT) features as shown by the absence of epithelial markers, such as E-cadherin, EpCAM, cytokeratin, and the presence of mesenchymal markers such as vimentin. Consistently, they have strong metastatic potential in vivo as observed in experimental metastasis models [11,38,39]. On the other hand, HCA24 cells have strong epithelial features and are highly differentiated cells that generate large xenografts in vivo without any evidence of metastasis generation [40].…”

Section: Gene Expression Profiling Of Esrp1-modulated Colo320dm and Hca24 Cellsmentioning

confidence: 54%

The RNA-Binding Protein ESRP1 Modulates the Expression of RAC1b in Colorectal Cancer Cells

Manco

Ala

Cantarella

et al. 2021

Cancers

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RNA binding proteins are well recognized as critical regulators of tumorigenic processes through their capacity to modulate RNA biogenesis, including alternative splicing, RNA stability and mRNA translation. The RNA binding protein Epithelial Splicing Regulatory Protein 1 (ESRP1) can act as a tumor suppressor or promoter in a cell type- and disease context-dependent manner. We have previously shown that elevated expression of ESRP1 in colorectal cancer cells can drive tumor progression. To gain further insights into the pro-tumorigenic mechanism of action of ESRP1, we performed cDNA microarray analysis on two colorectal cells lines modulated for ESRP1 expression. Intriguingly, RAC1b was highly expressed, both at mRNA and protein levels, in ESRP1-overexpressing cells, while the opposite trend was observed in ESRP1-silenced CRC cells. Moreover, RAC1 and RAC1b mRNA co-immunoprecipitate with ESRP1 protein. Silencing of RAC1b expression significantly reduced the number of soft agar colonies formed by ESRP1-overexpressing cells, suggesting that ESRP1 acted, at least partially, through RAC1b in its tumor-promoting activities in CRC cells. Thus, our data provide molecular cues on targetable candidates in CRC cases with high ESRP1 expression.

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Section: Gene Expression Profiling Of Esrp1-modulated Colo320dm and Hca24 Cellsmentioning

confidence: 54%

The RNA-Binding Protein ESRP1 Modulates the Expression of RAC1b in Colorectal Cancer Cells

Manco

Ala

Cantarella

et al. 2021

Cancers

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“…The MMP family is associated with tumour progression, metastasis and angiogenesis of CRC, and the overexpression of MMP‐2 and MMP‐9 has been known as a sign of poor prognostic factors 29 . Colo320DM cells lack the characteristics of forming dense cell colonies and are easily detached from culture plates due to few microvilli or desmosomes 30,31 . Thus, Colo320DM cells which have originally lost epithelial characteristics could cause low expression of EMT‐related factors other than MMP‐2.…”

Section: Discussionmentioning

confidence: 99%

Reduced chemokine C‐C motif ligand 1 expression may negatively regulate colorectal cancer progression at liver metastatic sites

Iwata,

Haraguchi,

Kitazawa

et al. 2024

J Cellular Molecular Medi

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Colorectal cancer (CRC) liver metastasis, albeit a stage‐IV disease, is completely curable by surgical resection in selected patients. In addressing the molecular basics of this phenomenon, differentially expressed genes at primary and liver metastatic sites were screened by RNA sequencing with the use of paraffin‐embedded surgical specimens. Chemokine C‐C motif ligand 1 (CCL1), a chemotactic factor for a ligand of the chemokine C‐C motif receptor 8 (CCR8), was isolated as one of the differentially expressed genes. Histological analysis revealed that the number of CCL1‐positive cells, mainly tumour associated macrophages (TAMs) located in the stroma of CRC, decreased significantly at liver metastatic sites, while the expression level of CCR8 on CRC remained unchanged. To explore the biological significance of the CCL1‐CCR8 axis in CRC, CCR8‐positive CRC cell line Colo320DM was used to assess the effect of the CCL1‐CCR8 axis on major signalling pathways, epithelial mesenchymal transition induction and cell motility. Upon stimulation of recombinant CCL1 (rCCL1), phosphorylation of AKT was observed in Colo320DM cells; on the other hand, the corresponding significant increase in MMP‐2 levels demonstrated by RT‐qPCR was nullified by siRNA (siCCR8). In the scratch test, rCCL1 treatment significantly increased the motility of Colo320DM cells, which was similarly nullified by siCCR8. Thus, the activation of the CCL1‐CCR8 axis is a positive regulator of CRC tumour progression. Reduced CCL1 expression of TAMs at liver metastatic sites may partly explain the unique slow tumour progression of CRC, thus providing for a grace period for radical resection of metastatic lesions.

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“…However, upon preliminary screening for tumor budding, only two models were selected for subsequent analysis: HT-29 and HCT-8, a high-grade and a low-grade budding model, respectively. Details regarding the models can be found in the papers of Tommelein and colleagues (8, 9).…”

Section: Methodsmentioning

confidence: 99%

Cell Line Derived Xenograft Mouse Models Are a Suitable in vivo Model for Studying Tumor Budding in Colorectal Cancer

et al. 2019

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Tumor budding (TB) is an important prognostic parameter in colorectal cancer (CRC) and associated with metastasis. However, the mechanisms of TB have not been fully elucidated and a major limitation is the absence of in vivo models. Here, we determine the suitability of human cell line derived xenografts (CDX) as models of TB in CRC. Pan-cytokeratin (CK)-stained next-generation Tissue Microarrays (ngTMA) of two CDX models (HT-29, n = 12 and HCT-8, n = 8) and human CRC ( n = 27 high-grade and 25 low-grade budding tumors, each) were evaluated for TB. Immunohistochemistry for E-cadherin, β-catenin, Ki-67, ZEB1, and TWIST1 was performed. HT-29 and HCT-8 were predominantly high-grade and no/low-grade TB tumors, respectively. TB counts in the tumor center (intratumoral budding, ITB) were significantly higher in HT-29 CDX tumors compared to human CRC ( p = 0.0099). No difference was found in TB counts at the invasion front (peritumoral budding, PTB; p =0.07). ITB and PTB were strongly correlated ( r = 0.438 and r = 0.62 in CDX and human CRC, respectively). Immunohistochemistry profiles were comparable in CDX and human CRC tissues. TB in the CDX mouse models is phenotypically similar to human CRCs and highlights comparable protein profiles. The HT-29 CDX could be a suitable model for the in vivo assessment of TB.

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Age and cellular context influence rectal prolapse formation in mice with caecal wall colorectal cancer xenografts

Cited by 5 publications

References 48 publications

The RNA-Binding Protein ESRP1 Modulates the Expression of RAC1b in Colorectal Cancer Cells

The RNA-Binding Protein ESRP1 Modulates the Expression of RAC1b in Colorectal Cancer Cells

Reduced chemokine C‐C motif ligand 1 expression may negatively regulate colorectal cancer progression at liver metastatic sites

Cell Line Derived Xenograft Mouse Models Are a Suitable in vivo Model for Studying Tumor Budding in Colorectal Cancer

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