XactMice: humanizing mouse bone marrow enables microenvironment reconstitution in a patient-derived xenograft model of head and neck cancer

Morton, J. Jason; Bird, Gregory; Keysar, Stephen B.; Astling, David P.; Lyons, Traci R.; Anderson, Ryan T.; Glogowska, Magdalena J.; Estes, Patricia A.; Eagles, Justin R.; Le, Phuong N.; Gan, Gregory N.; McGettigan, Brett; Fernandez, Pamela; Padilla-Just, Nuria; Varella‐Garcia, Marileila; Song, John I.; Bowles, Daniel W.; Schedin, Pepper; Tan, Aik‐Choon; Roop, Dennis R.; Wang, Xiaojing; Refaeli, Yosef; Jimeno, Antonio

doi:10.1038/onc.2015.94

Cited by 117 publications

(113 citation statements)

References 46 publications

(49 reference statements)

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“…40 The implantation of tumor cells in these mice permitted to highlight a specific immuno-response stimulated by the growth of the tumor. 42,43 Very recently, Morton et al 43 reported that by adding purified Tat-MYC and Tat-Bcl2 fusion proteins to cultured HSPCs the number of CD34+ cells markedly expanded, while transduced HSPCs retained the ability to differentiate into either myeloid or lymphoid cells, thus recapitulating both lineages of the human immune system. Interestingly, i n head and neck PDXs, the relationship between the tumor and immune system was similar to the one found in the patient in whom the tumor originated was observed.…”

Section: Mouse Species Advantages Limitationsmentioning

confidence: 99%

The role of mouse models in translational cancer research: present and future directions

Porru

Leonetti

2017

Transl Med Rep

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A major issue in the research for new anticancer therapeutics is represented by the low number of new compounds approved for clinical use in comparison to the good success rate reported in preclinical studies. This high attrition rate could be attributed to many factors including the unsatisfactory predictive value of experiments performed in animals. To this purpose, general opinions suggest that classical models as murine tumors and xenografts do not mimic the complexity of human cancer diseases and that the use and integration of different relevant mouse models could improve the efficiency of the drug development process. In this review, we overview the present state of research in the field of mouse models for cancer and describe the advantages and limitations of the different models. Finally, strategies for improving the predictive value of animal experiments will be also discussed.

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Section: Mouse Species Advantages Limitationsmentioning

confidence: 99%

The role of mouse models in translational cancer research: present and future directions

Porru

Leonetti

2017

Transl Med Rep

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“…Recently, lethally irradiated NOD SCID gamma mice humanized with cord blood hematopoietic stem cells (known as XactMice) were developed (Morton et al 2015). This model enables study of HNSCC in a microenvironment educated by human cytokines, T and B cells, and stroma.…”

Section: Tumor Immune Network and Relationship With Cancer Stem Cellsmentioning

confidence: 99%

Head and Neck Cancer Stem Cells

2015

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Head and neck squamous cell carcinoma (HNSCC) is the most common form of head and neck cancer. Annually, more than half a million individuals are diagnosed with this devastating disease, with increasing incidence in Europe and Southeast Asia. The diagnosis of HNSCC often occurs in late stages of the disease and is characterized by manifestation of a high-grade primary tumor and/or lymph node metastasis, precluding timely management of this deadly cancer. Recently, HNSCC cancer stem cells have emerged as an important factor for cancer initiation and maintenance of tumor bulk. Like normal stem cells, cancer stem cells can undergo self-renewal and differentiation. This unique trait allows for maintenance of the cancer stem cell pool and facilitates differentiation into heterogeneous neoplastic progeny when necessary. Recent studies have suggested coexistence of different cancer stem cell populations within a tumor mass, where the tumor initiation and metastasis properties of these cancer stem cells can be uncoupled. Cancer stem cells also possess resistant phenotypes that evade standard chemotherapy and radiotherapy, resulting in tumor relapse. Therefore, understanding distinctive pathways relating to cancer stem cells will provide insight into early diagnosis and treatment of HNSCC. In this review, we highlight current advances in identifying cancer stem cells, detail the interactions of these cells with the immune system within the tumor niche, and discuss the potential use of immunotherapy in managing HNSCC.Keywords: flow cytometry, tumor microenvironment, squamous cell carcinoma of the head and neck, neoplastic stem cells, tumor immunology, metastasis

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“…In this case, some murine growth factors and cytokines do not interact with their human counterpart receptors, orthotopic tumors vascularize more significantly than do subcutaneous tumors, and implantation to inguinal rather than thoracic fat pads show improved engraftment rates [44]. Humanization of tumor microenvironment to support tumor engraftment and growth [45] and its manipulation to narrow tumor-microenvironment gap [46] that recently produced Xactmice [47] are two interesting areas that add to the improved modeling of human tumors in mice.…”

Section: Generation Of Xenograft Modelsmentioning

confidence: 99%

Human Cancer Modeling: Recapitulating Tumor Heterogeneity Towards Personalized Medicine

Gardaneh

2017

mcij

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Despite diagnostic, preventive and therapeutic advances, the growing incidence of cancer and the high rate of mortality among patients affected by specific cancer types indicate that current clinical measures are not ideally useful in eradicating cancer. Chemoresistance and subsequent disease relapse are believed to be mainly driven by the cell-molecular heterogeneity of human tumors, which necessitate personalized approaches to deal with uniquely complex genetic profile of each patient's tumor. Such personalized medicinal therapies require dissection of cancer molecular profiles in order to profoundly understand the mechanisms underlying drug resistance and disease recurrence. Technological advances in comparative genome sequencing have begun to result in identification of common somatic mutations in specific cancer subtypes that potentially constitute bases for prognostic and diagnostic biomarkers and present novel therapeutic targets. These targets have to be tested in reliable platforms, so that data of drug responses obtained can be correlated with those responses elicited in origin by the parental tumor itself. Here, I reviewed different models of cancer in vitro and in vivo and outlined the utilization of these models in drug discovery and novel therapies of cancer with prospect for developing personalized anti-cancer strategies.

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XactMice: humanizing mouse bone marrow enables microenvironment reconstitution in a patient-derived xenograft model of head and neck cancer

Cited by 117 publications

References 46 publications

The role of mouse models in translational cancer research: present and future directions

The role of mouse models in translational cancer research: present and future directions

Head and Neck Cancer Stem Cells

Human Cancer Modeling: Recapitulating Tumor Heterogeneity Towards Personalized Medicine

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