An evolving story of the metastatic voyage of ovarian cancer cells: cellular and molecular orchestration of the adipose-rich metastatic microenvironment

Motohara, Takeshi; Masuda, Kenta; Morotti, Matteo; Zheng, Yiyan; El-Sahhar, Salma; Chong, Kay Y.; Wietek, Nina; Alsaadi, Abdulkhaliq; KaramiNejadRanjbar, Mohammad; Hu, Zhiyuan; Artibani, Mara; González, Laura Santana; Katabuchi, Hidetaka; Saya, Hideyuki; Ahmed, Ahmed A.

doi:10.1038/s41388-018-0637-x

Cited by 156 publications

(162 citation statements)

References 111 publications

(183 reference statements)

Supporting

Mentioning

151

Contrasting

Unclassified

Order By: Relevance

“…32). In addition, ovarian cancer metastasizes preferentially to the adipose-rich omentum (33). Omental fat possesses a distinct lipidomic signature with several lipid groups, including TAGs, DAGs, and SMs, showing differences when compared with subcutaneous fat (34).…”

Section: Triacylglyceridesmentioning

confidence: 99%

A Prospective Analysis of Circulating Plasma Metabolites Associated with Ovarian Cancer Risk

et al. 2020

View full text Add to dashboard Cite

◥ Ovarian cancer has few known risk factors, hampering identification of high-risk women. We assessed the association of prediagnostic plasma metabolites (N ¼ 420) with risk of epithelial ovarian cancer, including both borderline and invasive tumors. A total of 252 cases and 252 matched controls from the Nurses' Health Studies were included. Multivariable logistic regression was used to estimate ORs and 95% confidence intervals (CI), comparing the 90th-10th percentile in metabolite levels, using the permutationbased Westfall and Young approach to account for testing multiple correlated hypotheses. Weighted gene coexpression network analysis (WGCNA; n ¼ 10 metabolite modules) and metabolite set enrichment analysis (n ¼ 23 metabolite classes) were also evaluated. An increase in pseudouridine levels from the 10th to the 90th percentile was associated with a 2.5-fold increased risk of overall ovarian cancer (OR ¼ 2.56; 95% CI, 1.48-4.45; P ¼ 0.001/adjusted P ¼ 0.15); a similar risk estimate was observed for serous/poorly differentiated tumors (n ¼ 176 cases; comparable OR ¼ 2.38; 95% CI, 1.33-4.32; P ¼ 0.004/adjusted P ¼ 0.55). For nonserous tumors (n ¼ 34 cases), pseudouridine and C36:2 phosphatidylcholine plasmalogen had the strongest statistical associations (OR ¼ 9.84; 95% CI, 2.89-37.82; P < 0.001/adjusted P ¼ 0.07; and OR ¼ 0.11; 95% CI, 0.03-0.35; P < 0.001/adjusted P ¼ 0.06, respectively). Five WGCNA modules and 9 classes were associated with risk overall at FDR ≤ 0.20. Triacylglycerols (TAG) showed heterogeneity by tumor aggressiveness (case-only heterogeneity P < 0.0001). The TAG association with risk overall and serous tumors differed by acyl carbon content and saturation. In summary, this study suggests that pseudouridine may be a novel risk factor for ovarian cancer and that TAGs may also be important, particularly for rapidly fatal tumors, with associations differing by structural features. Significance: Pseudouridine represents a potential novel risk factor for ovarian cancer and triglycerides may be important particularly in rapidly fatal ovarian tumors.

show abstract

Section: Triacylglyceridesmentioning

confidence: 99%

A Prospective Analysis of Circulating Plasma Metabolites Associated with Ovarian Cancer Risk

et al. 2020

View full text Add to dashboard Cite

show abstract

“…This enables the tumor cells to avoid anoikis and acquire a more invasive phenotype. Macrophages have also been demonstrated to play an active role in the formation of spheroids [111]. The multicellular spheroids attach to the mesothelial cells using various cell adhesion molecules.…”

Section: Circulating Cancer Cells Form Clusters Through Tomo-and Hetementioning

confidence: 99%

Are Synapse-Like Structures a Possible Way for Crosstalk of Cancer with Its Microenvironment?

Alekseenko

Чернов

Kostrov

2020

Cancers

View full text Add to dashboard Cite

The failure of therapies directed at targets within cancer cells highlight the necessity for a paradigm change in cancer therapy. The attention of researchers has shifted towards the disruption of cancer cell interactions with the tumor microenvironment. A typical example of such a disruption is the immune checkpoint cancer therapy that disrupts interactions between the immune and the cancer cells. The interaction of cancer antigens with T cells occurs in the immunological synapses. This is characterized by several special features, i.e., the proximity of the immune cells and their target cells, strong intercellular adhesion, and secretion of signaling cytokines into the intercellular cleft. Earlier, we hypothesized that the cancer-associated fibroblasts interacting with cancer cells through a synapse-like adhesion might play an important role in cancer tumors. Studies of the interactions between cancer cells and cancer-associated fibroblasts showed that their clusterization on the membrane surface determined their strength and specificity. The hundreds of interacting pairs are involved in the binding that may indicate the formation of synapse-like structures. These interactions may be responsible for successful metastasis of cancer cells, and their identification and disruption may open new therapeutic possibilities.

show abstract

“…Further, several human studies reported suggestive associations of ovarian cancer risk with total cholesterol (45) (positive) or HDL (inverse) (46). Additionally, evidence has demonstrated that ovarian cancer metastasizes preferentially to the adipose-rich omentum, a key player in the creation of the metastatic tumor microenvironment in the intraperitoneal cavity (47). Omental fat possess a distinct lipidomic signature with several lipid groups, including TAGs, DAGs, and SMs, showing differences when compared to subcutaneous fat (48).…”

Section: Triacylglyceridesmentioning

confidence: 99%

“…Darker red shades represent higher overlap and similarity. Metabolite modules correspond to the squares along the diagonal.metastasizes preferentially to the adipose-rich omentum, a key player in the creation of the metastatic tumor microenvironment in the intraperitoneal cavity(47). Omental fat possess a distinct lipidomic signature with several lipid groups, including TAGs, DAGs, and SMs, showing differences when compared to subcutaneous fat(48).…”

mentioning

confidence: 99%

A prospective analysis of circulating plasma metabolomics and ovarian cancer risk

Zeleznik

Eliassen

Kraft

et al. 2019

Preprint

View full text Add to dashboard Cite

Statement of significance:Pseudouridine represents a potential novel risk factor for ovarian cancer. Triglycerides may play a key role in rapidly fatal ovarian tumors, with different associations by acyl carbon content and saturation.The authors declare no potential conflicts of interest.Please note that main figures and tables were placed in the body of the text after they have been referenced. Supplementary figures were placed after References. Supplementary tables were uploaded separately. AbstractWe assessed the association of pre-diagnostic plasma metabolites (N=420) with ovarian cancer risk. We included 252 cases and 252 matched controls from the Nurses' Health Studies.Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) comparing the 90 th -10 th percentile in metabolite levels, using permutation tests to account for testing multiple correlated hypotheses. Weighted gene co-expression network analysis (WGCNA) modules (n=10) and metabolite set enrichment analysis (MSEA; n=23) were also evaluated. Pseudouridine had the strongest statistical association with ovarian cancer risk overall (OR=2.56, 95%CI=1.48-4.45; p=0.001/adjusted-p=0.15). C36:2 phosphatidylcholine (PC) plasmalogen had the strongest statistical association with lower risk (OR=0.11, 95%CI=0.03-0.35; p<0.001/adjusted-p=0.06) and pseudouridine with higher risk (OR=9.84, 95%CI=2.89-37.82; p<0.001/adjusted-p=0.07) of non-serous tumors. Seven WGCNA modules and 15 classes were associated with risk at FDR≤0.20. Triacylglycerols (TAGs) showed heterogeneity by tumor aggressiveness (case-only heterogeneity-p<0.0001). TAG association with risk overall and serous tumors differed by acyl carbon content and saturation. Pseudouridine may be a novel risk factor for ovarian cancer. TAGs may also be important, particularly for rapidly fatal tumors, with associations differing by structural features. Validation in independent prospective studies and complementary experimental work to understand biological mechanisms is needed.

show abstract

An evolving story of the metastatic voyage of ovarian cancer cells: cellular and molecular orchestration of the adipose-rich metastatic microenvironment

Cited by 156 publications

References 111 publications

A Prospective Analysis of Circulating Plasma Metabolites Associated with Ovarian Cancer Risk

A Prospective Analysis of Circulating Plasma Metabolites Associated with Ovarian Cancer Risk

Are Synapse-Like Structures a Possible Way for Crosstalk of Cancer with Its Microenvironment?

A prospective analysis of circulating plasma metabolomics and ovarian cancer risk

Contact Info

Product

Resources

About