Induction of mouse tenascin expression by a human sarcomatoid wilms' tumor cell line growing in nude mice

Wilms tumor has been associated with genomic alterations at both the 11p13 and 11p15 regions. To differentiate between the involvement of these two loci, a chromosome 11 was constructed that had one or the other region deleted, and this chromosome was introduced into the tumorigenic Wilms tumor cell line G401. When assayed for tumor-forming activity in nude mice, the 11p13-deleted, but not the 11p15.5-p14.1-deleted chromosome, retained its ability to suppress tumor formation. These results provide in vivo functional evidence for the existence of a second genetic locus (WT2) involved in suppressing the tumorigenic phenotype of Wilms tumor.

Download Full-text

Preclinical evaluation of XPO1 inhibition in Wilms tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.3580 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 3580-3580

Author(s):

Michael Vincent Ortiz ◽

Armaan Siddiquee ◽

Daoqi You ◽

Prabhjot Singh Mundi ◽

Lianna Marks ◽

...

Keyword(s):

Tumor Cell ◽

Cell Line ◽

Nuclear Export ◽

Wilms Tumor ◽

Therapeutic Option ◽

Tumor Cell Line ◽

In Vivo Models ◽

Favorable Histology ◽

Rhabdoid Tumors ◽

1Q Gain

3580 Background: XPO1 is a nuclear export protein that selectively transports tumor and growth regulatory proteins out of the nucleus, thereby effectively inhibiting their function. We previously utilized the Virtual Inference of Protein-activity by Enriched Regulon analysis (VIPER) algorithm to discover that malignant rhabdoid tumors were dependent upon XPO1 inhibition and then evaluated a preclinical cohort using selinexor (KPT-330), the first-in-class selective inhibitor of nuclear export, to demonstrate that XPO1 inhibition was sufficient to cause cell cycle arrest, apoptosis, and disease control in multiple cell line and patient derived xenograft (PDXs) models. Our subsequent analysis revealed that the most common childhood kidney tumor, Wilms tumor, has even high higher inferred activity of XPO1 than rhabdoid tumors leading to our hypothesis that XPO1 inhibition is an effective therapeutic strategy to treat Wilms tumors. Methods: A panel of 9 Wilms tumor cell lines and 3 Wilms tumor PDXs were genomically characterized and tested to evaluate the pre-clinical efficacy of XPO1 inhibition in Wilms tumors. Results: Proliferation rate, increased XPO1 protein expression, and loss of function mutations in TP53 correlated with in vitro Wilms tumor cell line sensitivity to selinexor. Evaluation of co-segregation of all single nucleotide variant changes using with inferred activity of XPO1 on VIPER in all TGCA tumors demonstrates a strong association with TP53 alterations. XPO1 inhibition was effective in all Wilms tumor models tested, most significantly in MSKREN-57196, a favorable histology Wilms tumor PDX with somatic 1q gain as well as WTX and MYCN mutations, as well as in MSKREN-31827, a diffusely anaplastic TP53 mutant Wilms tumor PDX. Eltanexor (KPT-8602) is an XPO1 inhibitor with decreased CNS penetration and an improved toxicity profile; this drug was tested in these in vivo models and found to be at least as effective as selinexor. Conclusions: Somatic 1q gain in favorable histology Wilms tumors and TP53 mutations in diffusely anaplastic Wilms tumors have a particularly poor prognosis in the relapsed setting. Our study demonstrates that XPO1 inhibition may provide a rational therapeutic option to treat such high-risk Wilms tumors. Future clinical trials evaluating XPO1 inhibitors should evaluate its efficacy in children with relapsed Wilms tumors.

Download Full-text

Characterization of 17.94, a novel anaplastic Wilms' tumor cell line

Cancer Genetics ◽

10.1016/j.cancergen.2012.04.009 ◽

2012 ◽

Vol 205 (6) ◽

pp. 319-326 ◽

Cited By ~ 3

Author(s):

Keith W. Brown ◽

Adrian Charles ◽

Anthony Dallosso ◽

Gillian White ◽

Jessica Charlet ◽

...

Keyword(s):

Tumor Cell ◽

Cell Line ◽

Wilms Tumor ◽

Tumor Cell Line

Download Full-text

Establishment of a Conditionally Immortalized Wilms Tumor Cell Line with a Homozygous WT1 Deletion within a Heterozygous 11p13 Deletion and UPD Limited to 11p15

PLoS ONE ◽

10.1371/journal.pone.0155561 ◽

2016 ◽

Vol 11 (5) ◽

pp. e0155561 ◽

Cited By ~ 4

Author(s):

Artur Brandt ◽

Katharina Löhers ◽

Manfred Beier ◽

Barbara Leube ◽

Carmen de Torres ◽

...

Keyword(s):

Tumor Cell ◽

Cell Line ◽

Wilms Tumor ◽

Tumor Cell Line

Download Full-text

Introduction of a normal human chromosome 11 into a Wilms' tumor cell line controls its tumorigenic expression

Science ◽

10.1126/science.3031816 ◽

1987 ◽

Vol 236 (4798) ◽

pp. 175-180 ◽

Cited By ~ 242

Author(s):

B. Weissman ◽

P. Saxon ◽

Pasquale ◽

G. Jones ◽

A. Geiser ◽

...

Keyword(s):

Human Chromosome ◽

Tumor Cell ◽

Cell Line ◽

Wilms Tumor ◽

Tumor Cell Line ◽

Chromosome 11 ◽

Normal Human

Download Full-text

Establishment and characterization of HXWMF-1: the first mouse fibroblastic tumor cell line derived from leukemia-associated fibroblasts

Cancer Cell International ◽

10.1186/s12935-021-01870-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yuanyuan Li ◽

Ling Gu

Keyword(s):

Tumor Cell ◽

Cell Line ◽

Cancer Progression ◽

Nude Mice ◽

Lymphoblastic Leukemia ◽

Tumor Cell Line ◽

Culture Technique ◽

Str Analysis ◽

Response To Chemotherapy ◽

A Cell

Abstract Background Chemo-resistance is still a major obstacle in leukemia treatment. Accumulating evidence indicates that cancer-associated fibroblasts (CAFs), the most abundant stromal cells in tumor microenvironment (TME), play a crucial role in cancer progression and response to chemotherapy. To Figure out the role of leukemia-associated fibroblasts (LAFs) in relapsed/refractory leukemia, we constructed the first leukemia-associated fibroblastic tumor cell line, HXWMF-1. Methods A cell culture technique was used to establish the leukemia-associated fibroblastic tumor cell line. Molecular and cellular biological techniques including flow cytometry, MTT assay, western blotting, and short tandem repeat (STR) analysis were used to characterize the cell line. Nude mice were used for xenograft studies. Results We established a LAFs derived tumor cell line HXWMF-1, originated from the subcutaneous xenografts of HXEX-ALL1, a cell line originated from a patient with acute lymphoblastic leukemia (ALL) at the second relapse. The HXWMF-1 cell line was authenticated as a tumor cell line and being derived from CAFs based on morphologic, immunophenotypic, cytogenetic and STR analyses and tumorigenicity test in nude mice. To clarify the reliability of the method, we got the LAFs derived tumor cells from three different tumor mass of HXEX-ALL1 xenografts. Conclusions To our knowledge, HXWMF-1 is the first fibroblastic tumor cell line derived from LAFs or CAFs. In addition, the cell line provided firm evidence for that leukemia cells may induce LAFs/CAFs malignant transformation, which may help to develop brand new theory and therapeutic strategies for patients with relapsed /refractory ALL.

Download Full-text

Tumor cell line characterization of a malignant histiocytosis transplanted into nude mice

Virchows Archiv A Pathological Anatomy and Histology ◽

10.1007/bf00442387 ◽

1982 ◽

Vol 397 (2) ◽

pp. 171-181 ◽

Cited By ~ 13

Author(s):

M. F. Rousseau-Merck ◽

F. Jaubert ◽

M. A. Bach ◽

P. Niaudet ◽

D. Cottreau ◽

...

Keyword(s):

Tumor Cell ◽

Cell Line ◽

Nude Mice ◽

Tumor Cell Line ◽

Malignant Histiocytosis ◽

Cell Line Characterization

Download Full-text

Unexpected Preferential Brain Metastases with a Human Breast Tumor Cell Line MDA-MB-231 in BALB/c Nude Mice

Veterinary Pathology ◽

10.1354/vp.45-6-941 ◽

2008 ◽

Vol 45 (6) ◽

pp. 941-944 ◽

Cited By ~ 3

Author(s):

A. A. El-Mabhouh ◽

P. N. Nation ◽

A. Kaddoura ◽

J. R. Mercer

Keyword(s):

Breast Cancer ◽

Bone Metastasis ◽

Tumor Cell ◽

Cell Line ◽

Nude Mice ◽

Cancer Cell Line ◽

Tumor Cell Line ◽

Biological Behavior ◽

Intracardiac Injection ◽

New Treatments

Animal models are useful tools to study etiology, progress, and new treatments of disease and are an approximation of human disease for experimental study. Intracardiac injection of the human estrogen-independent breast cancer cell line MDA-MB-231 in nude mice is a well-characterized animal model of bone metastasis mainly used to study new treatments for late-stage breast cancer. According to the published literature, this model should produce radiologically distinguishable bone tumors within 17 days after injection. Mice should develop complications such as cachexia, paraplegia, and morbidity within 28 days and require euthanasia within 35 days after injection. We report a study in which injection of MDA-MB-231 cell line led to brain rather than bone metastasis. Unexpected alterations in biological behavior are an important confounding variable in the use of tumor cell lines, and the occurrence and cause of such variants is poorly documented.

Download Full-text