Immunophenotyping of an Unusual Mixed-Type Extraskeletal Osteosarcoma in a Dog

A 6-year-old female Maltese dog presented with a cervical mass without pain. The tumor was surrounded by a thick fibrous tissue and consisted of an osteoid matrix with osteoblasts and two distinct areas: a mesenchymal cell-rich lesion with numerous multinucleated giant cells and a chondroid matrix-rich lesion. The tumor cells exhibited heterogeneous protein expression, including a positive expression of vimentin, cytokeratin, RANKL, CRLR, SOX9, and collagen 2, and was diagnosed as extraskeletal osteosarcoma. Despite its malignancy, the dog showed no sign of recurrence or metastasis three months after the resection. Further analysis of the tumor cells revealed a high expression of proliferation- and metastasis-related biomarkers in the absence of angiogenesis-related biomarkers, suggesting that the lack of angiogenesis and the elevated tumor-associated fibrosis resulted in a hypoxic tumor microenvironment and prevented metastasis.

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EphA2 super-enhancer promotes tumor progression by recruiting FOSL2 and TCF7L2 to activate the target gene EphA2

Cell Death and Disease ◽

10.1038/s41419-021-03538-6 ◽

2021 ◽

Vol 12 (3) ◽

Author(s):

Shuang Cui ◽

Qiong Wu ◽

Ming Liu ◽

Mu Su ◽

ShiYou Liu ◽

...

Keyword(s):

Tumor Progression ◽

Tumor Cells ◽

Target Gene ◽

Super Enhancer ◽

Proliferation And Metastasis ◽

Active Transcription ◽

Hct 116 ◽

Large Clusters

AbstractSuper-enhancers or stretch enhancers (SEs) consist of large clusters of active transcription enhancers which promote the expression of critical genes that define cell identity during development and disease. However, the role of many super-enhancers in tumor cells remains unclear. This study aims to explore the function and mechanism of a new super-enhancer in various tumor cells. A new super-enhancer that exists in a variety of tumors named EphA2-Super-enhancer (EphA2-SE) was found using multiple databases and further identified. CRISPR/Cas9-mediated deletion of EphA2-SE results in the significant downregulation of its target gene EphA2. Mechanistically, we revealed that the core active region of EphA2-SE comprises E1 component enhancer, which recruits TCF7L2 and FOSL2 transcription factors to drive the expression of EphA2, induce cell proliferation and metastasis. Bioinformatics analysis of RNA-seq data and functional experiments in vitro illustrated that EphA2-SE deletion inhibited cell growth and metastasis by blocking PI3K/AKT and Wnt/β-catenin pathway in HeLa, HCT-116 and MCF-7 cells. Overexpression of EphA2 in EphA2-SE−/− clones rescued the effect of EphA2-SE deletion on proliferation and metastasis. Subsequent xenograft animal model revealed that EphA2-SE deletion suppressed tumor proliferation and survival in vivo. Taken together, these findings demonstrate that EphA2-SE plays an oncogenic role and promotes tumor progression in various tumors by recruiting FOSL2 and TCF7L2 to drive the expression of oncogene EphA2.

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Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice

Journal of Clinical Investigation ◽

10.1172/jci36843 ◽

2008 ◽

Cited By ~ 239

Author(s):

Pierre Sonveaux ◽

Frédérique Végran ◽

Thies Schroeder ◽

Melanie C. Wergin ◽

Julien Verrax ◽

...

Keyword(s):

Tumor Cells ◽

Hypoxic Tumor

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A cyanine-derived “turn-on” fluorescent probe for imaging nitroreductase in hypoxic tumor cells

Analytical Methods ◽

10.1039/c5ay02312b ◽

2015 ◽

Vol 7 (24) ◽

pp. 10125-10128 ◽

Cited By ~ 19

Author(s):

Cong Xue ◽

Yingjie Lei ◽

Sichun Zhang ◽

Yaowu Sha

Keyword(s):

Tumor Cells ◽

Fluorescent Probe ◽

Phenol Group ◽

Turn On ◽

Hypoxic Tumor

A new “turn-on” fluorescent probe, composed of a protected phenol group with ap-nitrobenzyl moiety that functions as a latent donor and conjugated with two benzo[f]indolinium acceptors, was developed and applied for imaging nitroreductase (NTR) in hypoxic tumor cells.

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Radiosensitization of hypoxic tumor cells by cis- and trans-dichlorodiammineplatinum (II)

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/0360-3016(79)90672-2 ◽

1979 ◽

Vol 5 (8) ◽

pp. 1369-1372 ◽

Cited By ~ 91

Author(s):

Evan B. Douple ◽

Robert C. Richmond

Keyword(s):

Tumor Cells ◽

Hypoxic Tumor ◽

Cis And Trans

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The Activity of KIF14, Mieap, and EZR in a New Type of the Invasive Component, Torpedo-Like Structures, Predetermines the Metastatic Potential of Breast Cancer

Cancers ◽

10.3390/cancers12071909 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1909

Author(s):

Tatiana S. Gerashchenko ◽

Sofia Y. Zolotaryova ◽

Artem M. Kiselev ◽

Liubov A. Tashireva ◽

Nikita M. Novikov ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Cells ◽

Cancer Metastasis ◽

Ether Lipid ◽

Metastatic Tumor ◽

Metastatic Potential ◽

Breast Cancer Metastasis ◽

Breast Cancers ◽

Invasive Component ◽

Positive Expression

Intratumor morphological heterogeneity reflects patterns of invasive growth and is an indicator of the metastatic potential of breast cancer. In this study, we used this heterogeneity to identify molecules associated with breast cancer invasion and metastasis. The gene expression microarray data were used to identify genes differentially expressed between solid, trabecular, and other morphological arrangements of tumor cells. Immunohistochemistry was applied to evaluate the association of the selected proteins with metastasis. RNA-sequencing was performed to analyze the molecular makeup of metastatic tumor cells. High frequency of metastases and decreased metastasis-free survival were detected in patients either with positive expression of KIF14 or Mieap or negative expression of EZR at the tips of the torpedo-like structures in breast cancers. KIF14- and Mieap-positive and EZR-negative cells were mainly detected in the torpedo-like structures of the same breast tumors; however, their transcriptomic features differed. KIF14-positive cells showed a significant upregulation of genes involved in ether lipid metabolism. Mieap-positive cells were enriched in genes involved in mitophagy. EZR-negative cells displayed upregulated genes associated with phagocytosis and the chemokine-mediated signaling pathway. In conclusion, the positive expression of KIF14 and Mieap and negative expression of EZR at the tips of the torpedo-like structures are associated with breast cancer metastasis.

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911: Molecular mechanisms of the antineoplastic action of erufosine in hypoxic tumor cells

European Journal of Cancer ◽

10.1016/s0959-8049(14)50810-6 ◽

2014 ◽

Vol 50 ◽

pp. S223

Author(s):

H. Riffkin ◽

S. Oeck ◽

G. Renzelman ◽

R. Handrick ◽

V. Jendrossek

Keyword(s):

Tumor Cells ◽

Molecular Mechanisms ◽

Antineoplastic Action ◽

Hypoxic Tumor

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δ-Tocotrienol treatment is more effective against hypoxic tumor cells than normoxic cells: potential implications for cancer therapy

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2015.02.011 ◽

2015 ◽

Vol 26 (8) ◽

pp. 832-840 ◽

Cited By ~ 8

Author(s):

Akira Shibata ◽

Kiyotaka Nakagawa ◽

Tsuyoshi Tsuduki ◽

Teruo Miyazawa

Keyword(s):

Cancer Therapy ◽

Tumor Cells ◽

Hypoxic Tumor

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Osseoinduction Evaluation of Hydroxyapatite and Zinc Containing Hydroxyapatite Granules in Rabbits

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.493-494.252 ◽

2011 ◽

Vol 493-494 ◽

pp. 252-257 ◽

Cited By ~ 1

Author(s):

L. Nascimento ◽

M. Medeiros ◽

J. Calasans-Maia ◽

A. Alves ◽

Antonella M. Rossi ◽

...

Keyword(s):

Histological Analysis ◽

Bone Matrix ◽

Fibrous Tissue ◽

Particle Diameter ◽

Inflammatory Cells ◽

Giant Cells ◽

Multinucleated Giant Cells ◽

Ethics Commission

This study investigated the osteoinductive potential of granules of stoichiometric hydroxyapatite (HA) and 0.5% zinc containing hydroxyapatite (ZnHA) in intramuscular (IM) site of rabbit’s abdomen. The biomaterials were both used in granular form, with 75% porosity and particle diameter between 450 and 500μm, sintered at 1100°C. Both materials performed adequately on a multiparametric in vitro cytocompatibility assay, indicating their suitability for in vivo testing. After approval by the Ethics Commission on Teaching and Research in Animals, fifteen rabbits were submitted to general anesthesia, incision and tissue dilatation, and a small site was created for HA (right incision) and ZnHA (left incision) intramuscular implantation. The animals were killed after 2, 4 and 12 weeks for biomaterials and surrounding tissues removal. Histological analysis after 2 weeks revealed the presence of granulation tissue surrounding biomaterials with multinucleated giant cells and no newly formed bone for both materials. After 4 weeks there was fibrous tissue involving the material and few inflammatory cells. Following 12 weeks it was observed the presence of connective tissue surrounding the biomaterial, cellularized enough for the two experimental groups, but it was not observed the presence of bone matrix associated with the biomaterials. We conclude that both biomaterials are cytocompatible and did not present the property of osseoinduction after 12 weeks of implantation.

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