Establishment and characterization of HROC69 – a Crohn´s related colonic carcinoma cell line and its matched patient-derived xenograft

Kuehn, Florian; Mullins, Christina Susanne; Krohn, Mathias; Harnack, Christine; Ramer, Robert; Krämer, Oliver; Klar, E.; Huehns, Maja; Linnebacher, Michael

doi:10.1038/srep24671

Cited by 9 publications

(7 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An additional restraint arises from the very limited functional data included in the present manuscript. Several of the HROC cell lines as well as PDX models have already been published [14,26,27,28,29]. For the PDX collection, a subset of >100 cases is currently under detailed analysis and this study will be published soon.…”

Section: Discussionmentioning

confidence: 99%

Integrated Biobanking and Tumor Model Establishment of Human Colorectal Carcinoma Provides Excellent Tools for Preclinical Research

Mullins

Micheel

Matschos

et al. 2019

Cancers

Self Cite

View full text Add to dashboard Cite

Over the time period from 2006 to 2017, consecutive patients operated on at the University Medical Center Rostock participated in the comprehensive biobanking and tumor-modelling approach known as the HROC collection. Samples were collected using strict standard operating procedures including blood (serum and lymphocytes), tumor tissue (vital and snap frozen), and adjacent normal epithelium. Patient and tumor data including classification, molecular type, clinical outcome, and results of the model establishment are the essential pillars. Overall, 149 patient-derived xenografts with 34 primary and 35 secondary cell lines were successfully established and encompass all colorectal carcinoma anatomic sites, grading and staging types, and molecular classes. The HROC collection represents one of the largest model assortments from consecutive clinical colorectal carcinoma (CRC) cases worldwide. Statistical analysis identified a variety of clinicopathological and molecular factors associated with model success in univariate analysis. Several of them not identified before include localization, mutational status of K-Ras and B-Raf, MSI-status, and grading and staging parameters. In a multivariate analysis model, success solely correlated positively with the nodal status N1 and mutations in the genes K-Ras and B-Raf. These results imply that generating CRC tumor models on the individual patient level is worth considering especially for advanced tumor cases with a dismal prognosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Integrated Biobanking and Tumor Model Establishment of Human Colorectal Carcinoma Provides Excellent Tools for Preclinical Research

Mullins

Micheel

Matschos

et al. 2019

Cancers

Self Cite

View full text Add to dashboard Cite

show abstract

“…We here addressed the question to which extent mERV are activated and possibly transmitted to human CRC cells when passaged as PDX in immunodeficient mice. Technically, this approach was possible due to a large collection of low-passage, patient-derived tumor models including PDX and matching tumor- and PDX-derived permanent cell lines ( Maletzki et al, 2015 ; Gock et al, 2016 ; Kuehn et al, 2016 ; Mullins et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Murine Endogenous Retroviruses Are Detectable in Patient-Derived Xenografts but Not in Patient-Individual Cell Lines of Human Colorectal Cancer

et al. 2018

Self Cite

View full text Add to dashboard Cite

Endogenous retroviruses are remnants of retroviral infections. In contrast to their human counterparts, murine endogenous retroviruses (mERV) still can synthesize infectious particles and retrotranspose. Xenotransplanted human cells have occasionally been described to be mERV infected. With genetic engineered mice and patient-derived xenografts (PDXs) on the rise as eminent research tools, we here systematically investigated, if different tumor models harbor mERV infections. Relevant mERV candidates were first preselected by next generation sequencing (NGS) analysis of spontaneous lymphomas triggered by colorectal cancer (CRC) PDX tissue. Two primer systems were designed for each of these candidates (AblMLV, EcoMLV, EndoPP, MLV, and preXMRV) and implemented in an quantitative real-time (RT-qPCR) screen using murine tissues (n = 11), PDX-tissues (n = 22), PDX-derived cell lines (n = 13), and patient-derived tumor cell lines (n = 14). The expression levels of mERV varied largely both in the PDX samples and in the mouse tissues. No mERV signal was, however, obtained from cDNA or genomic DNA of CRC cell lines. Expression of EcoMLV was higher in PDX than in murine tissues; for EndoPP it was the opposite. These two were thus further investigated in 40 additional PDX. In addition, four patient-derived cell lines free of any mERV expression were subcutaneously injected into immunodeficient mice. Outgrowing cell-derived xenografts barely expressed EndoPP. In contrast, the expression of EcoMLV was even higher than in surrounding mouse tissues. This expression gradually vanished within few passages of re-cultivated cells. In summary, these results strongly imply that: (i) PDX and murine tissues in general are likely to be contaminated by mERV, (ii) mERV are expressed transiently and at low level in fresh PDX-derived cell cultures, and (iii) mERV integration into the genome of human cells is unlikely or at least a very rare event. Thus, mERVs are stowaways present in murine cells, in PDX tissues and early thereof-derived cell cultures. We conclude that further analysis is needed concerning their impact on results obtained from studies performed with PDX but also with murine tumor models.

show abstract

“…These were treated with 3 nM Muristerone A (MurA, Alexis Biochemicals, USA) for 24 hours to induce p21; details on these cells are explained [ 42 ]. HROC43, HROC239 T0 M1 and HROBMC01 were generated and cultured as described [ 60 , 61 ]. Early passages below 40 were used.…”

Section: Methodsmentioning

confidence: 99%

Survivin antagonizes chemotherapy-induced cell death of colorectal cancer cells

et al. 2018

Self Cite

View full text Add to dashboard Cite

Irinotecan (CPT-11) and oxaliplatin (L-OHP) are among the most frequently used drugs against colorectal tumors. Therefore, it is important to define the molecular mechanisms that these agents modulate in colon cancer cells. Here we demonstrate that CPT-11 stalls such cells in the G2/M phase of the cell cycle, induces an accumulation of the tumor suppressor p53, the replicative stress/DNA damage marker γH2AX, phosphorylation of the checkpoint kinases ATM and ATR, and an ATR-dependent accumulation of the pro-survival molecule survivin. L-OHP reduces the number of cells in S-phase, stalls cell cycle progression, transiently triggers an accumulation of low levels of γH2AX and phosphorylated checkpoint kinases, and L-OHP suppresses survivin expression at the mRNA and protein levels. Compared to CPT-11, L-OHP is a stronger inducer of caspases and p53-dependent apoptosis. Overexpression and RNAi against survivin reveal that this factor critically antagonizes caspase-dependent apoptosis in cells treated with CPT-11 and L-OHP. We additionally show that L-OHP suppresses survivin through p53 and its downstream target p21, which stalls cell cycle progression as a cyclin-dependent kinase inhibitor (CDKi). These data shed new light on the regulation of survivin by two clinically significant drugs and its biological and predictive relevance in drug-exposed cancer cells.

show abstract

Establishment and characterization of HROC69 – a Crohn´s related colonic carcinoma cell line and its matched patient-derived xenograft

Cited by 9 publications

References 41 publications

Integrated Biobanking and Tumor Model Establishment of Human Colorectal Carcinoma Provides Excellent Tools for Preclinical Research

Integrated Biobanking and Tumor Model Establishment of Human Colorectal Carcinoma Provides Excellent Tools for Preclinical Research

Murine Endogenous Retroviruses Are Detectable in Patient-Derived Xenografts but Not in Patient-Individual Cell Lines of Human Colorectal Cancer

Survivin antagonizes chemotherapy-induced cell death of colorectal cancer cells

Contact Info

Product

Resources

About