41 research outputs found
Abstract 3977: Neutrophils fertilize the pre-metastatic omental niche in ovarian cancer
No full textAbstract
More than 60% of ovarian cancer patients present with peritoneal carcinomatosis that almost always involves the omentum, a fat pad that suspends from the stomach. However, the mechanisms that promote the tropism of ovarian cancer cells for the omentum are poorly understood. Because the omentum is the major peritoneal conduit and reservoir for immune cells, we hypothesized that immune cells control the propensity of ovarian cancer cells to implant on the omentum. In this study, we evaluated changes in immune cell populations in the omentum and in other visceral fat pads in the peritoneal cavity in mouse xenograft models of ovarian cancer. Intriguingly, the proportion of neutrophils was observed to dramatically increase in the omentum prior to tumor cell implantation at this site. On the other hand, the proportion of neutrophils did not substantially increase in other visceral fat pads. Furthermore, the proportion of macrophages did not significantly increase in any of the fat tissues prior to tumor cell implantation. Collectively, these findings raise the possibility that early recruitment of neutrophils to the pre-metastatic omental niche promotes a microenvironment that is conducive to ovarian cancer cell implantation at this site.
Citation Format: WonJae LEE, Honami Naora. Neutrophils fertilize the pre-metastatic omental niche in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3977. doi:10.1158/1538-7445.AM2017-3977</jats:p
Abstract 783: Cancer cell-derived extracellular vesicles stimulate tumor angiogenesis by delivering VEGF to endothelial cells
No full textAbstract
Angiogenesis is essential for tumor growth and metastasis, and is orchestrated by a repertoire of growth factor signaling pathways that stimulate endothelial cell growth, migration and vessel formation. Recent studies have shown that angiogenesis can also be regulated by cell-derived extracellular vesicles. Exosomes are small endosomal-derived membrane vesicles that contain various biomolecules such as RNA and proteins, and are increasingly thought to play important roles in transferring informational cargo between cancer cells and stromal cells. In the majority of studies to date, the effects of cancer cell-derived exosomes have been attributed to their RNA cargo. In this study, we identified that exosomes derived from ovarian, colon and renal cancer cells contain abundant vascular endothelial growth factor (VEGF). Cancer cell-derived exosomes were found to activate the VEGF signaling pathway in endothelial cells and to stimulate endothelial cell migration and tube formation. Furthermore, our studies using inhibitors of VEGF signaling demonstrated that the stimulatory effects of cancer cell-derived exosomes on endothelial cells depend on the presence of VEGF in exosomes and are mediated via the VEGF signaling pathway. These findings indicate that cancer cell-derived exosomes promote tumor angiogenesis by delivering VEGF to endothelial cells.
Citation Format: Song Yi Ko, Honami Naora. Cancer cell-derived extracellular vesicles stimulate tumor angiogenesis by delivering VEGF to endothelial cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 783. doi:10.1158/1538-7445.AM2017-783</jats:p
Heterotypic Cellular Interactions in the Ovarian Tumor Microenvironment: Biological Significance and Therapeutic Implications
No full textThe majority of women who are diagnosed with epithelial ovarian cancer present with extensive peritoneal carcinomatosis and are rarely cured by conventional chemotherapy. Ovarian cancer cells typically disseminate by shedding into the peritoneal fluid and implant on the mesothelium-lined peritoneal surfaces that overlie connective and white adipose tissues. Emerging evidence indicates that ovarian tumor progression is orchestrated by dynamic interplay between tumor cells and a variety of stromal cells such as adipocytes, endothelial cells, fibroblasts, mesenchymal stem cells, macrophages and other immune cells. This mini-review discusses the biological significance of the heterotypic cellular interactions in the ovarian tumor microenvironment and the therapeutic implications of targeting these interactions
Involvement of ribosomal proteins in regulating cell growth and apoptosis: Translational modulation or recruitment for extraribosomal activity?
No full text
Developmental Patterning in the Wrong Context: The Paradox of Epithelial Ovarian Cancers
No full textRevisiting the Use of Normal Saline for Peritoneal Washing in Ovarian Cancer
No full textThe omentum is the predominant site of ovarian cancer metastasis, but it is difficult to remove the omentum in its entirety. There is a critical need for effective approaches that minimize the risk of colonization of preserved omental tissues by occult cancer cells. Normal saline (0.9% sodium chloride) is commonly used to wash the peritoneal cavity during ovarian cancer surgery. The omentum has a prodigious ability to absorb fluid in the peritoneal cavity, but the impact of normal saline on the omentum is poorly understood. In this review article, we discuss why normal saline is not a biocompatible solution, drawing insights from clinical investigations of normal saline in fluid resuscitation and from the cytopathologic evaluation of peritoneal washings. We integrate these insights with the unique biology of the omentum and omental metastasis, highlighting the importance of considering the absorptive ability of the omentum when administering agents into the peritoneal cavity. Furthermore, we describe insights from preclinical studies regarding the mechanisms by which normal saline might render the omentum conducive for colonization by cancer cells. Importantly, we discuss the possibility that the risk of colonization of preserved omental tissues might be minimized by using balanced crystalloid solutions for peritoneal washing
HOXA9 promotes homotypic and heterotypic cell interactions that facilitate ovarian cancer dissemination via its induction of P-cadherin
No full textExtracellular Vesicle Membrane-Associated Proteins: Emerging Roles in Tumor Angiogenesis and Anti-Angiogenesis Therapy Resistance
No full textThe tumor vasculature is essential for tumor growth and metastasis, and is a prime target of several anti-cancer agents. Increasing evidence indicates that tumor angiogenesis is stimulated by extracellular vesicles (EVs) that are secreted or shed by cancer cells. These EVs encapsulate a variety of biomolecules with angiogenic properties, and have been largely thought to stimulate vessel formation by transferring this luminal cargo into endothelial cells. However, recent studies have revealed that EVs can also signal to recipient cells via proteins on the vesicular surface. This review discusses and integrates emerging insights into the diverse mechanisms by which proteins associate with the EV membrane, the biological functions of EV membrane-associated proteins in tumor angiogenesis, and the clinical significance of these proteins in anti-angiogenic therapy
