Phenotypic differentiation does not affect tumorigenicity of primary human colon cancer initiating cells

Dubash, Taronish D.; Hoffmann, Christopher M.; Oppel, F.; Giessler, Klara M.; Weber, Sarah; Dieter, Sebastian M.; Hüllein, Jennifer; Zenz, Thorsten; Herbst, Friederike; Scholl, Claudia; Weichert, Wilko; Werft, Wiebke; Benner, Axel; Schmidt, Manfred; Schneider, Martin; Glimm, Hanno; Ball, Claudia R.

doi:10.1016/j.canlet.2015.11.037

Cited by 11 publications

(19 citation statements)

References 30 publications

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“…The purification and culture of colorectal cancer cells was performed as previously described . In brief, tumor samples were mechanically dissociated and incubated with Dispase (BD Biosciences).…”

Section: Methodsmentioning

confidence: 99%

Patient-derived xenografts of gastrointestinal cancers are susceptible to rapid and delayed B-lymphoproliferation

et al. 2017

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Patient-derived cancer xenografts (PDX) are widely used to identify and evaluate novel therapeutic targets, and to test therapeutic approaches in preclinical mouse avatar trials. Despite their widespread use, potential caveats of PDX models remain considerably underappreciated. Here, we demonstrate that EBV-associated B-lymphoproliferations frequently develop following xenotransplantation of human colorectal and pancreatic carcinomas in highly immunodeficient NOD.Cg-Prkdc Il2rg /SzJ (NSG) mice (18/47 and 4/37 mice, respectively), and in derived cell cultures in vitro. Strikingly, even PDX with carcinoma histology can host scarce EBV-infected B-lymphocytes that can fully overgrow carcinoma cells during serial passaging in vitro and in vivo. As serial xenografting is crucial to expand primary tumor tissue for biobanks and cohorts for preclinical mouse avatar trials, the emerging dominance of B-lymphoproliferations in serial PDX represents a serious confounding factor in these models. Consequently, repeated phenotypic assessments of serial PDX are mandatory at each expansion step to verify "bona fide" carcinoma xenografts.

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Section: Methodsmentioning

confidence: 99%

Patient-derived xenografts of gastrointestinal cancers are susceptible to rapid and delayed B-lymphoproliferation

et al. 2017

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“…The use of PDX techniques in murine engineered systems represents one of the more advanced investigation tools for cancer research as it supports the areas of therapeutics, personalized medicine, drug screening, biomarker development and co-clinical trials [ 133 ]. GEMMs have become the main recipients for PDXs and are extensively used for translational investigations by the pharmaceutical industry and in academic research [ 134 – 136 ].…”

Section: Mice Models In Primary Culture Researchmentioning

confidence: 99%

Management and potentialities of primary cancer cultures in preclinical and translational studies

et al. 2017

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The use of patient-derived primary cell cultures in cancer preclinical assays has increased in recent years. The management of resected tumor tissue remains complex and a number of parameters must be respected to obtain complete sample digestion and optimal vitality yield. We provide an overview of the benefits of correct primary cell culture management using different preclinical methodologies, and describe the pros and cons of this model with respect to other kinds of samples. One important advantage is that the heterogeneity of the cell populations composing a primary culture partially reproduces the tumor microenvironment and crosstalk between malignant and healthy cells, neither of which is possible with cell lines. Moreover, the use of patient-derived specimens in innovative preclinical technologies, such as 3D systems or bioreactors, represents an important opportunity to improve the translational value of the results obtained. In vivo models could further our understanding of the crosstalk between tumor and other tissues as they enable us to observe the systemic and biological interactions of a complete organism. Although engineered mice are the most common model used in this setting, the zebrafish (Danio rerio) species has recently been recognized as an innovative experimental system. In fact, the transparent body and incomplete immune system of zebrafish embryos are especially useful for evaluating patient-derived tumor tissue interactions in healthy hosts. In conclusion, ex vivo systems represent an important tool for cancer research, but samples require correct manipulation to maximize their translational value.

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“…Examples for markers that gave controversial results are CD133 and Lgr5 (Table 1 ). Over the last years, many reports have challenged the view of CD133 being a universal TIC marker [ 40 – 43 ]. Importantly, several in vivo studies show that CD133 + and CD133 − cells form tumors with similar efficiency [ 40 , 43 , 44 ].…”

Section: Isolation and Identification Of Ticsmentioning

confidence: 99%

“…Over the last years, many reports have challenged the view of CD133 being a universal TIC marker [ 40 – 43 ]. Importantly, several in vivo studies show that CD133 + and CD133 − cells form tumors with similar efficiency [ 40 , 43 , 44 ]. Over the last years, Lgr5 has been revealed as a marker for normal and cancerous intestinal stem cells [ 7 , 45 ].…”

Section: Isolation and Identification Of Ticsmentioning

confidence: 99%

Tumor-Initiating Cells: a criTICal review of isolation approaches and new challenges in targeting strategies

et al. 2017

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Most cancers contain a subpopulation of highly tumorigenic cells, known as cancer stem cells (CSCs) or tumor-initiating cells (TICs). Targeting TICs may be essential to achieve cure, because of their self-renewal and tumorigenic properties as well as their resistance to conventional therapies. Despite significant advances in TIC biology, their isolation and identification remain largely disputed and incompletely established. In this review, we discuss the latest developments in isolation and culturing approaches of TICs, with focus on colorectal cancer (CRC). We feature recent findings on TIC-relevant signaling pathways and the metabolic identity of TICs, as well as their current clinical implications. Lastly, we highlight the influence of inter- and intra-tumoral heterogeneity on TIC function and targeting approaches.

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Phenotypic differentiation does not affect tumorigenicity of primary human colon cancer initiating cells

Cited by 11 publications

References 30 publications

Patient-derived xenografts of gastrointestinal cancers are susceptible to rapid and delayed B-lymphoproliferation

Patient-derived xenografts of gastrointestinal cancers are susceptible to rapid and delayed B-lymphoproliferation

Management and potentialities of primary cancer cultures in preclinical and translational studies

Tumor-Initiating Cells: a criTICal review of isolation approaches and new challenges in targeting strategies

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