Isolation and characterization of stromal progenitor cells from ascites of patients with epithelial ovarian adenocarcinoma

Ho, Chih‐Ming; Chang, Shwu-Fen; Hsiao, C. C.; Chien, Tsai-Yen; Shih, Daniel Tzu-Bi

doi:10.1186/1423-0127-19-23

Cited by 50 publications

(50 citation statements)

References 35 publications

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“…3 A and B). Malignant ascites contains a mix of tumor cells and other cell types as well proteinaceous secretions (11)(12)(13)(14)(15). The concentration of ovarian cancer cells in this milieu likely changes as the disease progresses and the volume of ascites increases.…”

Section: Tumor Growth Under Continuous Flowmentioning

confidence: 99%

“…The buildup of ascites occurs when the rate of fluid production exceeds the rate of clearance, typically because of an underlying pathology such as cancer. Multiple factors drive the accumulation of this transudate, including the overproduction of peritoneal fluid, increased leakiness of tumor microvasculature, and obstruction of lymphatic vessels (11)(12)(13)(14)(15). The abnormal buildup of protein-and cell-rich ascitic fluid in the peritoneal cavity occurs frequently in ovarian cancer and is associated with a dismal quality of life and a grim median survival (7,11).…”

mentioning

confidence: 99%

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Flow induces epithelial-mesenchymal transition, cellular heterogeneity and biomarker modulation in 3D ovarian cancer nodules

Rizvi

Gürkan

Tasoğlu

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

206

229

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Seventy-five percent of patients with epithelial ovarian cancer present with advanced-stage disease that is extensively disseminated intraperitoneally and prognosticates the poorest outcomes. Primarily metastatic within the abdominal cavity, ovarian carcinomas initially spread to adjacent organs by direct extension and then disseminate via the transcoelomic route to distant sites. Natural fluidic streams of malignant ascites triggered by physiological factors, including gravity and negative subdiaphragmatic pressure, carry metastatic cells throughout the peritoneum. We investigated the role of fluidic forces as modulators of metastatic cancer biology in a customizable microfluidic platform using 3D ovarian cancer nodules. Changes in the morphological, genetic, and protein profiles of biomarkers associated with aggressive disease were evaluated in the 3D cultures grown under controlled and continuous laminar flow. A modulation of biomarker expression and tumor morphology consistent with increased epithelial-mesenchymal transition, a critical step in metastatic progression and an indicator of aggressive disease, is observed because of hydrodynamic forces. The increase in epithelial-mesenchymal transition is driven in part by a posttranslational up-regulation of epidermal growth factor receptor (EGFR) expression and activation, which is associated with the worst prognosis in ovarian cancer. A flowinduced, transcriptionally regulated decrease in E-cadherin protein expression and a simultaneous increase in vimentin is observed, indicating increased metastatic potential. These findings demonstrate that fluidic streams induce a motile and aggressive tumor phenotype. The microfluidic platform developed here potentially provides a flow-informed framework complementary to conventional mechanism-based therapeutic strategies, with broad applicability to other lethal malignancies.tumor microenvironment | stress response | molecular targets | combination therapies | photodynamic therapy C ancer metastases are responsible for 90% of cancer-related deaths, but the biological and physical factors that determine the fate and heterogeneity of metastatic tumors remain poorly understood (1-6). Ovarian cancer is the leading cause of deaths related to gynecologic malignancies, and is frequently diagnosed at an advanced stage. Initially, ovarian cancer metastasizes by direct extension to sites that are proximal to the primary tumor through a complex series of events including migration, assembly, and proliferation (7-10). Dissemination to distant sites prognosticates the poorest outcomes for ovarian cancer patients and occurs via transcoelomic, lymphatic, or hematogenous routes (7,9,10). Among these routes, transcoelomic metastases are the most frequent and are responsible for the highest morbidity and mortality rates, which in turn are associated with the frequent production of malignant ascites (7, 9, 10). Under normal physiologic conditions, the great majority of peritoneal fluid is resorbed by the vasculature and the lymphatics and...

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Section: Tumor Growth Under Continuous Flowmentioning

confidence: 99%

mentioning

confidence: 99%

Flow induces epithelial-mesenchymal transition, cellular heterogeneity and biomarker modulation in 3D ovarian cancer nodules

Rizvi

Gürkan

Tasoğlu

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

206

229

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“…However, long-term survival of patients with advanced EOC remains limited. 3 Further investigation of the molecular mechanism of EOC metastasis is necessary to find ways to control the EOC metastasis.…”

mentioning

confidence: 99%

Effect of Down-Regulated Transcriptional Repressor ZEB1 on the Epithelial-Mesenchymal Transition of Ovarian Cancer Cells

Chen

Wang

Zhang

et al. 2013

International Journal of Gynecological Cancer

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“…[81]. These cells also express genes responsible for tumorigenesis and metastasis: BMP-2, BMP4, TGF-β, EGFR, and integrin α 2 β 1 [23].…”

Section: Malignant Ascites-cellular Factorsmentioning

confidence: 99%

Ascitic Fluid in Ovarian Carcinoma – From Pathophysiology to the Treatment

Živadinović¹,

Petrić²,

Krtinić³

et al. 2017

Ascites - Physiopathology, Treatment, Complications and Prognosis

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Due to low symptomatology, a lack of screening, and relatively complicated diagnostic procedures of ovarian carcinoma, more and more women are believed to visit their doctors in advanced stage of the disease, complicated with ascitic fluid. There is an increasing evidence that peritoneal cytology is a subjective assessment with certain percentage of false-positive and false-negative results that may cause application of unnecessary chemotherapy or nonapplication of necessary chemotherapy. Maximal cytoreductive surgery followed by intraperitoneal or systemic chemotherapy remains to be the gold standard in preventing ascites. Ascites is not only a symptom of a disease, but a specific microenvironment for formation and mediation of protumorigenic signals that control ovarian cancer progression, proliferation, invasion, anti-apoptosis, chemoresistance and tumor heterogeneity. Acellular cytokines and immunological factors influence ovarian cancer progression and its ability to prevent immune responses of the body and tumor reaction to chemotherapy. Ascites contributes to disease dissemination, changing its course and final outcomes. Management of patients with ascites and ovarian carcinoma is complex and often the goal of the treatment is to target palliative procedures. Multidisciplinary approach is necessary in the management of these patients. Further investigations of new drugs and immunomodulators are needed aiming at prolonged periods between relapses.

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Isolation and characterization of stromal progenitor cells from ascites of patients with epithelial ovarian adenocarcinoma

Cited by 50 publications

References 35 publications

Flow induces epithelial-mesenchymal transition, cellular heterogeneity and biomarker modulation in 3D ovarian cancer nodules

Flow induces epithelial-mesenchymal transition, cellular heterogeneity and biomarker modulation in 3D ovarian cancer nodules

Effect of Down-Regulated Transcriptional Repressor ZEB1 on the Epithelial-Mesenchymal Transition of Ovarian Cancer Cells

Ascitic Fluid in Ovarian Carcinoma – From Pathophysiology to the Treatment

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