Cell–cell and cell–matrix dynamics in intraperitoneal cancer metastasis

Sodek, Katharine L.; Murphy, Kate; Brown, Theodore J.; Ringuette, Maurice J.

doi:10.1007/s10555-012-9351-2

Cited by 128 publications

(168 citation statements)

References 160 publications

(214 reference statements)

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“…This mesothelial layer is highly receptive to ovarian cancer seeding [66]. Implantation of spheroids on the peritoneum involves interactions between cancer cells and the mesothelium.…”

Section: How Does the Tumor Environment Afect Eoc Dissemination?mentioning

confidence: 99%

Ascites in Ovarian Cancer Progression: Opportunities for Biomarker Discovery and New Avenues for Targeted Therapies

Matte¹,

Bessette²,

Piché³

2017

Ascites - Physiopathology, Treatment, Complications and Prognosis

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Until recently, ovarian cancer research has mainly focused on the tumor cell themselves ignoring for the most part the surrounding tumor environment. However, one of the major conceptual advances in oncology over the last few years has been the appreciation that major aspects of cancer biology are inluenced by the tumor environment. Malignant ascites accumulates in the peritoneal cavity during ovarian cancer progression and constitutes a unique pro-inlammatory tumor environment providing a framework that orchestrates cellular and molecular changes contributing to aggressiveness and disease progression. The composition of ascites, which includes cellular and acellular components, constantly adapts during the course of the disease in response to various cellular cues originating from both tumor and stromal cells. Increasing evidence now supports an active role of ascites in the progression of ovarian cancer. Although much work is still needed to fully understand the contribution of ascites to ovarian cancer aggressiveness, this tumor environment potentially provides a wealth of opportunities for translational research including biomarker discovery and novel therapeutic target identiication. In this review, we discuss recent advances in our understanding of ascites pathophysiology, the characterization of its cellular and acellular contents, the intercellular crosstalks, and how these data can be used to improve the outcome of ovarian cancer.

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“…This mesothelial layer is highly receptive to ovarian cancer seeding [66]. Implantation of spheroids on the peritoneum involves interactions between cancer cells and the mesothelium.…”

Section: How Does the Tumor Environment Afect Eoc Dissemination?mentioning

confidence: 99%

Ascites in Ovarian Cancer Progression: Opportunities for Biomarker Discovery and New Avenues for Targeted Therapies

Matte¹,

Bessette²,

Piché³

2017

Ascites - Physiopathology, Treatment, Complications and Prognosis

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“…The three-dimensional tumor spheroid model has been suggested to represent an in vitro system similar to that of micrometastases [26]. In fact, it has been suggested that certain cancers utilize endogenous spheroid formation to survive transit through the peritoneal cavity to sites of metastasis [18]. In addition, recent studies have shown that metastases require the support of stromal cells for continuous growth and propagation [1][2][3].…”

Section: Discussionmentioning

confidence: 99%

“…Tumor spheroids mimic the structure of metastatic lesions and are more relevant for assessing drug delivery than monolayer cultures [17,18]. We have shown previously that human serum albumin (HSA) nanoconjugates with multiple arginine-glycine-aspartic acid (RGD) peptides are able to effectively penetrate and distribute in a tumor spheroid model [19].…”

Section: Introductionmentioning

confidence: 99%

Tumor Cell–Targeted Delivery of Nanoconjugated Oligonucleotides in Composite Spheroids

Carver

Xin²,

Juliano³

2014

Nucleic Acid Therapeutics

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Standard tissue culture has often been a poor model for predicting the efficacy of anti-cancer agents including oligonucleotides. In contrast to the simplicity of monolayer tissue cultures, a tumor mass includes tightly packed tumor cells, tortuous blood vessels, high levels of extracellular matrix, and stromal cells that support the tumor. These complexities pose a challenge for delivering therapeutic agents throughout the tumor, with many drugs limited to cells proximal to the vasculature. Multicellular tumor spheroids are superior to traditional monolayer cell culture for the assessment of cancer drug delivery, since they possess many of the characteristics of metastatic tumor foci. However, homogeneous spheroids comprised solely of tumor cells do not account for some of the key aspects of metastatic tumors, particularly the interaction with host cells such as fibroblasts. Further, homogeneous culture does not allow for the assessment of targeted delivery to tumor versus host cells. Here we have evaluated delivery of targeted and untargeted oligonucleotide nanoconjugates and of oligonucleotide polyplexes in both homogeneous and composite tumor spheroids. We find that inclusion of fibroblasts in the spheroids reduces delivery efficacy of the polyplexes. In contrast, targeted multivalent RGD-oligonucleotide nanoconjugates were able to effectively discriminate between melanoma cells and fibroblasts, thus providing tumor-selective uptake and pharmacological effects.

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“…In addition, several studies have indicated that exosomes derived from cancer cells cause the proliferation and transformation of PMCs [56]. In the process of peritoneal metastasis, normal PMCs become carcinoma-associated fibroblasts.…”

Section: The Potential Relevance Between Exosomes and Pmcsmentioning

confidence: 99%

Exosomes: The New Mediator of Peritoneal Membrane Function

Shi

Sheng³

2018

Kidney Blood Press Res

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Fibrosis and angiogenesis are the most common processes that result in progressive peritoneal tissue remodeling and, eventually, peritoneal membrane dysfunction. The role of exosomes, which contributes to intercellular communication, in these processes has been neglected. Various biomolecules, including DNA, mRNA, proteins, lipids, and particular certain miRNAs, can be transferred by exosomes to local, neighboring and distal cells. Upon stimulation by cytokines or other microenvironment stimuli, donor cells release a mass of exosomes to peritoneal mesothelial cells, further affecting fibrosis and angiogenesis. This important exosomes-mediated intracellular communication is thought to regulate peritoneal membrane function. Understanding the molecular mechanisms of these processes, targeting changes in exosomes and regulating exosomal miRNAs will advance therapeutic methods for protecting peritoneal membrane function.

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Cell–cell and cell–matrix dynamics in intraperitoneal cancer metastasis

Cited by 128 publications

References 160 publications

Ascites in Ovarian Cancer Progression: Opportunities for Biomarker Discovery and New Avenues for Targeted Therapies

Ascites in Ovarian Cancer Progression: Opportunities for Biomarker Discovery and New Avenues for Targeted Therapies

Tumor Cell–Targeted Delivery of Nanoconjugated Oligonucleotides in Composite Spheroids

Exosomes: The New Mediator of Peritoneal Membrane Function

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