scholarly journals Selectins: An Important Family of Glycan-Binding Cell Adhesion Molecules in Ovarian Cancer

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2238
Author(s):  
Ayon A. Hassan ◽  
Margarita Artemenko ◽  
Maggie K.S. Tang ◽  
Alice S.T. Wong
Keyword(s):  
Ovarian Cancer ◽  
Peritoneal Cavity ◽  
Cancer Metastasis ◽  
Cell Interaction ◽  
Gynecological Malignancy ◽  
Selectin Ligand ◽  
Cancer Dissemination ◽  
Tumor Types ◽  
Potential Therapeutic Intervention ◽  
Binding Cell

Ovarian cancer is the most lethal gynecological malignancy worldwide. Unlike most other tumor types that metastasize via the vasculature, ovarian cancer metastasizes predominantly via the transcoelomic route within the peritoneal cavity. As cancer metastasis accounts for the majority of deaths, there is an urge to better understand its determinants. In the peritoneal cavity, tumor-mesothelial adhesion is an important step for cancer dissemination. Selectins are glycan-binding molecules that facilitate early steps of this adhesion cascade by mediating heterotypic cell-cell interaction under hydrodynamic flow. Here, we review the function and regulation of selectins in peritoneal carcinomatosis of ovarian cancer, and highlight how dysregulation of selectin ligand biogenesis affects disease outcome. Further, we will introduce the latest tools in studying selectin-glycan interaction. Finally, an overview of potential therapeutic intervention points that may lead to the development of efficacious therapies for ovarian cancer is provided.

scholarly journals MicroRNA in Ovarian Cancer: Biology, Pathogenesis, and Therapeutic Opportunities

2019 ◽  
Vol 16 (9) ◽  
pp. 1510 ◽  
Author(s):  
San-Nung Chen ◽  
Renin Chang ◽  
Li-Te Lin ◽  
Chyi-Uei Chern ◽  
Hsiao-Wen Tsai ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Messenger Rna ◽  
Cancer Biology ◽  
Cancer Metastasis ◽  
Female Reproductive System ◽  
Future Perspectives ◽  
Action Current ◽  
Cellular Processes ◽  
New Biomarkers ◽  
Tumor Types

Ovarian cancer comprises one of the three major malignant tumor types in the female reproductive system. The mortality rate of this cancer is the highest among all gynecological tumors, with ovarian cancer metastasis constituting an important cause of death. Therefore, markers for disease prediction and prognosis are highly desirable for early diagnosis as well as for helping optimize and personalize treatment. Recently, microRNAs (miRNAs), which consist of short-sequence RNAs that do not encode a protein, have emerged as new biomarkers in the clinical diagnosis and treatment of ovarian cancer. By pairing with bases specific to the target messenger RNA (mRNA), miRNAs cause degradation of the target mRNA or inhibit its translation, thereby regulating various cellular processes including cell proliferation and adhesion. Increasing numbers of studies have shown that miRNA expression abnormality plays an important role in the development of ovarian cancer. In this review, we discuss the mechanisms of miRNA action, current research regarding their role in the suppression or promotion of ovarian cancer, and their use as markers for diagnosis of prognosis or as therapeutic targets for this disease. Finally, we present future perspectives regarding the clinical management of ovarian cancer and the role for miRNAs therein.

scholarly journals A Novel Role for NUAK1 in Promoting Ovarian Cancer Metastasis through Regulation of Fibronectin Production in Spheroids

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1250 ◽  
Author(s):  
Jamie Lee Fritz ◽  
Olga Collins ◽  
Parima Saxena ◽  
Adrian Buensuceso ◽  
Yudith Ramos Valdes ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Metastasis ◽  
Primary Tumour ◽  
Xenograft Model ◽  
Cell Interaction ◽  
Spheroid Formation ◽  
Gene Encoding ◽  
Fibronectin Expression ◽  
Liver Kinase B1 ◽  
Expression Pathways

Epithelial ovarian cancer (EOC) has a unique mode of metastasis, where cells shed from the primary tumour, form aggregates called spheroids to evade anoikis, spread through the peritoneal cavity, and adhere to secondary sites. We previously showed that the master kinase Liver kinase B1 (LKB1) is required for EOC spheroid viability and metastasis. We have identified novel (nua) kinase 1 (NUAK1) as a top candidate LKB1 substrate in EOC cells and spheroids using a multiplex inhibitor beads-mass spectrometry approach. We confirmed that LKB1 maintains NUAK1 phosphorylation and promotes its stabilization. We next investigated NUAK1 function in EOC cells. Ectopic NUAK1-overexpressing EOC cell lines had increased adhesion, whereas the reverse was seen in OVCAR8-NUAK1KO cells. In fact, cells with NUAK1 loss generate spheroids with reduced integrity, leading to increased cell death after long-term culture. Following transcriptome analysis, we identified reduced enrichment for cell interaction gene expression pathways in OVCAR8-NUAK1KO spheroids. In fact, the FN1 gene, encoding fibronectin, exhibited a 745-fold decreased expression in NUAK1KO spheroids. Fibronectin expression was induced during native spheroid formation, yet this was completely lost in NUAK1KO spheroids. Co-incubation with soluble fibronectin restored the compact spheroid phenotype to OVCAR8-NUAK1KO cells. In a xenograft model of intraperitoneal metastasis, NUAK1 loss extended survival and reduced fibronectin expression in tumours. Thus, we have identified a new mechanism controlling EOC metastasis, through which LKB1-NUAK1 activity promotes spheroid formation and secondary tumours via fibronectin production.

scholarly journals A systematic CRISPR screen reveals an IL-20/IL20RA-mediated immune crosstalk to prevent the ovarian cancer metastasis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jia Li ◽  
Xuan Qin ◽  
Jie Shi ◽  
Xiaoshuang Wang ◽  
Tong Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Peritoneal Cavity ◽  
Cancer Metastasis ◽  
Immune Surveillance ◽  
Mesothelial Cells ◽  
Downstream Signaling ◽  
Key Factor ◽  
Crispr Screen

Transcoelomic spread of cancer cells across the peritoneal cavity occurs in most initially diagnosed ovarian cancer (OC) patients and accounts for most cancer-related death. However, how OC cells interact with peritoneal stromal cells to evade the immune surveillance remains largely unexplored. Here, through an in vivo genome-wide CRISPR/Cas9 screen, we identified IL20RA, which decreased dramatically in OC patients during peritoneal metastasis, as a key factor preventing the transcoelomic metastasis of OC. Reconstitution of IL20RA in highly metastatic OC cells greatly suppresses the transcoelomic metastasis. OC cells, when disseminate into the peritoneal cavity, greatly induce peritoneum mesothelial cells to express IL-20 and IL-24, which in turn activate the IL20RA downstream signaling in OC cells to produce mature IL-18, eventually resulting in the polarization of macrophages into the M1-like subtype to clear the cancer cells. Thus, we show an IL-20/IL20RA-mediated crosstalk between OC and mesothelial cells that supports a metastasis-repressing immune microenvironment.

scholarly journals WOMEN IN CANCER THEMATIC REVIEW: Ovarian cancer–peritoneal cell interactions promote extracellular matrix processing

2016 ◽  
Vol 23 (11) ◽  
pp. T155-T168 ◽  
Author(s):  
C Ricciardelli ◽  
N A Lokman ◽  
M P Ween ◽  
M K Oehler
Keyword(s):  
Ovarian Cancer ◽  
Extracellular Matrix ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Cell Interaction ◽  
Peritoneal Cell ◽  
Ovarian Cancer Cells ◽  
Peritoneal Cells ◽  
Proteomic Approach

Ovarian cancer has a distinct tendency for metastasising via shedding of cancerous cells into the peritoneal cavity and implanting onto the peritoneum that lines the pelvic organs. Once ovarian cancer cells adhere to the peritoneal cells, they migrate through the peritoneal layer and invade the local organs. Alterations in the extracellular environment are critical for tumour initiation, progression and intra-peritoneal dissemination. To increase our understanding of the molecular mechanisms involved in ovarian cancer metastasis and to identify novel therapeutic targets, we recently studied the interaction of ovarian cancer and peritoneal cells using a proteomic approach. We identified several extracellular matrix (ECM) proteins including, fibronectin, TGFBI, periostin, annexin A2 and PAI-1 that were processed as a result of the ovarian cancer–peritoneal cell interaction. This review focuses on the functional role of these proteins in ovarian cancer metastasis. Our findings together with published literature support the notion that ECM processing via the plasminogen–plasmin pathway promotes the colonisation and attachment of ovarian cancer cells to the peritoneum and actively contributes to the early steps of ovarian cancer metastasis.

scholarly journals Cellular and molecular processes in ovarian cancer metastasis. A Review in the Theme: Cell and Molecular Processes in Cancer Metastasis

2015 ◽  
Vol 309 (7) ◽  
pp. C444-C456 ◽  
Author(s):  
Tsz-Lun Yeung ◽  
Cecilia S. Leung ◽  
Kay-Pong Yip ◽  
Chi Lam Au Yeung ◽  
Stephen T. C. Wong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Survival Rate ◽  
Cancer Cells ◽  
Primary Tumor ◽  
Cancer Metastasis ◽  
Hematogenous Metastasis ◽  
Ovarian Cancer Cells ◽  
Molecular Processes ◽  
Lower Survival Rate ◽  
Gynecological Malignancy

Ovarian cancer is the most lethal gynecological malignancy. It is usually diagnosed at a late stage, with a 5-yr survival rate of <30%. The majority of ovarian cancer cases are diagnosed after tumors have widely spread within the peritoneal cavity, limiting the effectiveness of debulking surgery and chemotherapy. Owing to a substantially lower survival rate at late stages of disease than at earlier stages, the major cause of ovarian cancer deaths is believed to be therapy-resistant metastasis. Although metastasis plays a crucial role in promoting ovarian tumor progression and decreasing patient survival rates, the underlying mechanisms of ovarian cancer spread have yet to be thoroughly explored. For many years, researchers have believed that ovarian cancer metastasizes via a passive mechanism by which ovarian cancer cells are shed from the primary tumor and carried by the physiological movement of peritoneal fluid to the peritoneum and omentum. However, the recent discovery of hematogenous metastasis of ovarian cancer to the omentum via circulating tumor cells instigated rethinking of the mode of ovarian cancer metastasis and the importance of the “seed-and-soil” hypothesis for ovarian cancer metastasis. In this review we discuss the possible mechanisms by which ovarian cancer cells metastasize from the primary tumor to the omentum, the cross-talk signaling events between ovarian cancer cells and various stromal cells that play crucial roles in ovarian cancer metastasis, and the possible clinical implications of these findings in the management of this deadly, highly metastatic disease.

Adipose-derived stem cells in ovarian cancer progression, metastasis, and chemoresistance

2021 ◽  
pp. 153537022110238
Author(s):  
Wenjing Zhang ◽  
Carolina Torres-Rojas ◽  
Junming Yue ◽  
Bing-Mei Zhu
Keyword(s):  
Ovarian Cancer ◽  
Stem Cell ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Early Stage ◽  
Ovarian Cancer Cells ◽  
High Recurrence Rate ◽  
Gynecological Malignancy ◽  
Adipose Derived Stem Cell

Ovarian cancer is the deadliest gynecological malignancy due to its symptomless early stage, metastasis, and high recurrence rate. The tumor microenvironment contributes to the ovarian cancer progression, metastasis, and chemoresistance. Adipose-derived stem cell in the tumor microenvironment of ovarian cancer, as a key player, interacts with ovarian cancer cells to form the cancer-associated fibroblasts and cancer-associated adipocytes, and secretes soluble factors to activate tumor cell signaling, which can promote ovarian cancer metastasis and chemoresistance. We summarize in this review the recent progress in the studies of interactions between adipose-derived stem cell and ovarian cancer, thus, to provide some insight for ovarian cancer therapy through targeting adipose-derived stem cell.

scholarly journals Host Mesothelin Expression Increases Ovarian Cancer Metastasis in the Peritoneal Microenvironment

2021 ◽  
Vol 22 (22) ◽  
pp. 12443
Author(s):  
Tyvette S. Hilliard ◽  
Brooke Kowalski ◽  
Kyle Iwamoto ◽  
Elizabeth A. Agadi ◽  
Yueying Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Peritoneal Cavity ◽  
Cancer Metastasis ◽  
Single Cells ◽  
Mesothelial Cell ◽  
Metastatic Tumor ◽  
Tumor Burden ◽  
Mesothelial Cells ◽  
Stage Disease

Mesothelin (MSLN), a glycoprotein normally expressed by mesothelial cells, is overexpressed in ovarian cancer (OvCa) suggesting a role in tumor progression, although the biological function is not fully understood. OvCa has a high mortality rate due to diagnosis at advanced stage disease with intraperitoneal metastasis. Tumor cells detach from the primary tumor as single cells or multicellular aggregates (MCAs) and attach to the mesothelium of organs within the peritoneal cavity producing widely disseminated secondary lesions. To investigate the role of host MSLN in the peritoneal cavity we used a mouse model with a null mutation in the MSLN gene (MSLNKO). The deletion of host MSLN expression modified the peritoneal ultrastructure resulting in abnormal mesothelial cell surface architecture and altered omental collagen fibril organization. Co-culture of murine OvCa cells with primary mesothelial cells regardless of MSLN expression formed compact MCAs. However, co-culture with MSLNKO mesothelial cells resulted in smaller MCAs. An allograft tumor study, using wild-type mice (MSLNWT) or MSLNKO mice injected intraperitoneally with murine OvCa cells demonstrated a significant decrease in peritoneal metastatic tumor burden in MSLNKO mice compared to MSLNWT mice. Together, these data support a role for host MSLN in the progression of OvCa metastasis.

scholarly journals A systematic CRISPR screen reveals an IL-20/IL20RA-mediated peritoneal immune crosstalk to prevent the ovarian cancer metastasis

2021 ◽  
Author(s):  
Jia Li ◽  
Xuan Qin ◽  
Jie Shi ◽  
Xiaoshuang Wang ◽  
Tong Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Peritoneal Cavity ◽  
Cancer Metastasis ◽  
Immune Surveillance ◽  
Mesothelial Cells ◽  
Downstream Signaling ◽  
Key Factor ◽  
Crispr Screen

AbstractTranscoelomic spread of cancer cells across the peritoneal cavity occurs in most initially diagnosed ovarian cancer (OC) patients and accounts for most cancer-related death. However, how OC cells interact with peritoneal stromal cells to evade the immune surveillance remains largely unexplored. Here, through an in vivo genome-wide CRISPR/Cas9 screen, we identified IL20RA, which decreased dramatically in OC patients during peritoneal metastasis, as a key factor preventing the transcoelomic metastasis of OC. Reconstitution of IL20RA in highly metastatic OC cells greatly suppresses the transcoelomic metastasis. OC cells, when disseminate into the peritoneal cavity, greatly induce peritoneum mesothelial cells to express IL-20 and IL-24, which in turn activate the IL20RA downstream signaling in OC cells to produce mature IL-18, eventually resulting in the polarization of macrophages into the M1-like subtype to clear the cancer cells. Thus, we show an IL-20/IL20RA-mediated crosstalk between OC and mesothelial cells that supports a metastasis-repressing immune microenvironment.

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