scholarly journals Hormonal Regulation of Patient-Derived Endometrial Cancer Stem-like Cells Generated by Three-Dimensional Culture

Endocrinology ◽  
2019 ◽  
Vol 160 (8) ◽  
pp. 1895-1906 ◽  
Author(s):  
Sachiko Shiba ◽  
Kazuhiro Ikeda ◽  
Takashi Suzuki ◽  
Daisuke Shintani ◽  
Koji Okamoto ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Hormonal Regulation ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Three Dimensional ◽  
Metastatic Tumor ◽  
Receptor Expression ◽  
Low Grade ◽  
17Β Estradiol ◽  
Pdx Models

Abstract Low-grade and early-stage endometrial cancer usually has a favorable prognosis, whereas recurrent or metastatic disease is often difficult to cure. Thus, the molecular mechanisms underlying advanced pathophysiology remain to be elucidated. From the perspective of the origin of advanced endometrial cancer, the characterization of cancer stem-like cells (CSCs) will be the first step toward the development of clinical management. We established long-term culturable patient-derived cancer cells (PDCs) from patient endometrial tumors by spheroid cell culture, which is favorable for the enrichment of CSCs. PDC-derived xenograft tumors were generated in immunodeficient NOD/Shi-scid, IL-2RγKO Jic mice. Morphologically, PDCs derived from three distinct patient samples and their xenograft tumors recapitulated the corresponding original patient tumors. Of note, CSC-related genes including ALDH1A1 were upregulated in all of these PDCs, and the therapeutic potentiality of aldehyde dehydrogenase inhibitors was demonstrated. In addition, these PDCs and their patient-derived xenograft (PDX) models exhibited distinct characteristics on the basis of their hormone responsiveness and metastatic features. Interestingly, genes associated with inflammation and tumor immunity were upregulated by 17β-estradiol in PDC lines with high estrogen receptor expression and were also overexpressed in secondary PDCs obtained from metastatic tumor models. These results suggest that PDC and PDX models from endometrial cancer specimens would be useful to elucidate CSC traits and to develop alternative diagnostic and therapeutic options for advanced disease.

Ovarian conservation for young women with early-stage low-grade endometrial cancer: A proposal for a two-step approach

2021 ◽  
Author(s):  
Koji Matsuo ◽  
Rachel S. Mandelbaum ◽  
Shinya Matsuzaki ◽  
Maximilian Klar ◽  
Lynda D. Roman ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Young Women ◽  
Early Stage ◽  
Low Grade ◽  
Ovarian Conservation

scholarly journals Distinct roles for paxillin and Hic-5 in regulating breast cancer cell morphology, invasion, and metastasis

2011 ◽  
Vol 22 (3) ◽  
pp. 327-341 ◽  
Author(s):  
Nicholas O. Deakin ◽  
Christopher E. Turner
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Morphology ◽  
Molecular Mechanisms ◽  
Adhesion Formation ◽  
Three Dimensional ◽  
Rho Kinase ◽  
Adaptor Protein ◽  
Metastatic Tumor

Individual metastatic tumor cells exhibit two interconvertible modes of cell motility during tissue invasion that are classified as either mesenchymal or amoeboid. The molecular mechanisms by which invasive breast cancer cells regulate this migratory plasticity have yet to be fully elucidated. Herein we show that the focal adhesion adaptor protein, paxillin, and the closely related Hic-5 have distinct and unique roles in the regulation of breast cancer cell lung metastasis by modulating cell morphology and cell invasion through three-dimensional extracellular matrices (3D ECMs). Cells depleted of paxillin by RNA interference displayed a highly elongated mesenchymal morphology, whereas Hic-5 knockdown induced an amoeboid phenotype with both cell populations exhibiting reduced plasticity, migration persistence, and velocity through 3D ECM environments. In evaluating associated signaling pathways, we determined that Rac1 activity was increased in cells devoid of paxillin whereas Hic-5 silencing resulted in elevated RhoA activity and associated Rho kinase–induced nonmuscle myosin II activity. Hic-5 was essential for adhesion formation in 3D ECMs, and analysis of adhesion dynamics and lifetime identified paxillin as a key regulator of 3D adhesion assembly, stabilization, and disassembly.

scholarly journals Unique Molecular Features in High-Risk Histology Endometrial Cancers

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1665 ◽  
Author(s):  
Pooja Pandita ◽  
Xiyin Wang ◽  
Devin E. Jones ◽  
Kaitlyn Collins ◽  
Shannon M. Hawkins
Keyword(s):  
Endometrial Cancer ◽  
High Risk ◽  
Early Stage ◽  
Standard Of Care ◽  
The United States ◽  
Model Systems ◽  
Low Grade ◽  
Cell Of Origin ◽  
Molecular Features ◽  
The Impact

Endometrial cancer is the most common gynecologic malignancy in the United States and the sixth most common cancer in women worldwide. Fortunately, most women who develop endometrial cancer have low-grade early-stage endometrioid carcinomas, and simple hysterectomy is curative. Unfortunately, 15% of women with endometrial cancer will develop high-risk histologic tumors including uterine carcinosarcoma or high-grade endometrioid, clear cell, or serous carcinomas. These high-risk histologic tumors account for more than 50% of deaths from this disease. In this review, we will highlight the biologic differences between low- and high-risk carcinomas with a focus on the cell of origin, early precursor lesions including atrophic and proliferative endometrium, and the potential role of stem cells. We will discuss treatment, including standard of care therapy, hormonal therapy, and precision medicine-based or targeted molecular therapies. We will also discuss the impact and need for model systems. The molecular underpinnings behind this high death to incidence ratio are important to understand and improve outcomes.

scholarly journals CTNNB1 (beta-catenin) mutation identifies low grade, early stage endometrial cancer patients at increased risk of recurrence

2017 ◽  
Vol 30 (7) ◽  
pp. 1032-1041 ◽  
Author(s):  
Katherine C Kurnit ◽  
Grace N Kim ◽  
Bryan M Fellman ◽  
Diana L Urbauer ◽  
Gordon B Mills ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Low Grade ◽  
Beta Catenin ◽  
Risk Of Recurrence ◽  
Increased Risk ◽  
Early Stage Endometrial Cancer

scholarly journals Endometrial Cancer: What Is New in Adjuvant and Molecularly Targeted Therapy?

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Flora Zagouri ◽  
George Bozas ◽  
Eftichia Kafantari ◽  
Marinos Tsiatas ◽  
Nikitas Nikitas ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Metastatic Disease ◽  
Cancer Biology ◽  
Early Stage ◽  
Single Agent ◽  
Postoperative Management ◽  
Low Grade ◽  
Early Stage Disease ◽  
High Risk Factors ◽  
Staging Surgery

Endometrial cancer is the most common gynaecological cancer in western countries. Radiotherapy remains the mainstay of postoperative management, but accumulating data show that adjuvant chemotherapy may display promising results after staging surgery. The prognosis of patients with metastatic disease remains disappointing with only one-year survival. Progestins represent an effective option, especially for those patients with low-grade estrogen and/or progesterone receptor positive disease. Chemotherapy using the combination of paclitaxel, doxorubicin, and cisplatin is beneficial for patients with advanced or metastatic disease after staging surgery and potentially for patients with early-stage disease and high-risk factors. Toxicity is a point in question; however, the combination of paclitaxel with carboplatin may diminish these concerns. In women with multiple medical comorbidities, single-agent chemotherapy may be better tolerated with acceptable results. Our increased knowledge of the molecular aspects of endometrial cancer biology has paved the way for clinical research to develop novel targeted antineoplastic agents (everolimus, temsirolimus, gefitinib, erlotinib, cetuximab, trastuzumab, bevacizumab, sorafenib) as more effective and less toxic options. Continued investigation into the molecular pathways of endometrial cancer development and progression will increase our knowledge of this disease leading to the discovery of novel, superior agents.

scholarly journals Ovarian Conservation and Overall Survival in Young Women With Early-Stage Low-Grade Endometrial Cancer

2016 ◽  
Vol 128 (4) ◽  
pp. 761-770 ◽  
Author(s):  
Koji Matsuo ◽  
Hiroko Machida ◽  
Donna Shoupe ◽  
Alexander Melamed ◽  
Laila I. Muderspach ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Young Women ◽  
Early Stage ◽  
Low Grade ◽  
Ovarian Conservation
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