Tumor cell‑fibroblast heterotypic aggregates in�malignant ascites of patients with ovarian cancer

Han, Qing; Huang, Bangxing; Huang, Zaiju; Cai, Jing; Gong, Lanqing; Zhang, Yifan; Jiang, Jiahong; Wu, Dong; Wang, Zehua

doi:10.3892/ijmm.2019.4361

Cited by 26 publications

(26 citation statements)

References 36 publications

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“…These findings indicate that cells in the intraperitoneal microenvironment transduce signals and interact with each other. Consistent with previous research 38 , we found that various cell types exist in the ascites population, including cancer cells, CAFs and macrophagocytes (Supplementary Fig. 3 ).…”

Section: Discussionsupporting

confidence: 92%

Exosomes in ovarian cancer ascites promote epithelial–mesenchymal transition of ovarian cancer cells by delivery of miR-6780b-5p

Cai

Gong

et al. 2021

Cell Death Dis

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The poor prognosis of ovarian cancer is mainly due to metastasis, and the specific mechanism underlying ovarian cancer metastasis is not clear. Ascites-derived exosomes (ADEs) play an important role in the progression of ovarian cancer, but the mechanism is unknown. Here, we found that ADEs promoted ovarian cancer metastasis not only in vitro but also in vivo. This promotive function was based on epithelial–mesenchymal transition (EMT) of ovarian cancer cells. Bioinformatics analysis of RNA sequencing microarray data indicated that miR-6780b-5p may be the key microRNA (miRNA) in ADEs that facilitates cancer metastasis. Moreover, the expression of exosomal miR-6780b-5p correlated with tumor metastasis in ovarian cancer patients. miR-6780b-5p overexpression promoted and miR-6780b-5p downregulation suppressed EMT of ovarian cancer cells. These results suggest that ADEs transfer miR-6780b-5p to ovarian cancer cells, promoting EMT and finally facilitating ovarian cancer metastasis.

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Section: Discussionsupporting

confidence: 92%

Exosomes in ovarian cancer ascites promote epithelial–mesenchymal transition of ovarian cancer cells by delivery of miR-6780b-5p

Cai

Gong

et al. 2021

Cell Death Dis

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“…CAFs associated with HGSOC contribute to the formation of heterotypic spheroids in the malignant ascites [80]. Those CAFs-centered spheroids recruits floating ovarian cancer cells, resulting in the formation of 'metastatic units' at early stages of transcoelomic metastasis [80,81]. Mechanistically, floating ovarian cancer cells drive the production and secretion of EGF by CAFs located at the center region of the spheroids.…”

Section: More Recently Gao Et Al Have Demonstrated Thatmentioning

confidence: 99%

Regulation of heterogeneous cancer-associated fibroblasts: the molecular pathology of activated signaling pathways

Yoshida

2020

J Exp Clin Cancer Res

176

146

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Accumulating evidence indicates that intratumoral heterogeneity contributes to the development of resistance to anticancer therapeutics. Fibroblasts, which are components of the paraneoplastic stroma, play a crucial role in the wound-healing process. Activated fibroblasts accumulate in the wound and are involved in many aspects of the tissue remodeling cascade that initiates the repair process and prevents further tissue damage. The pathophysiological roles of cancer-associated fibroblasts (CAFs) in the heterogeneous tumor microenvironment have attracted increasing interest. CAFs play crucial roles in tumor progression and the response to chemotherapy. Several cytokines and chemokines are involved in the conversion of normal fibroblasts into CAFs, and some of these form a feedback loop between cancer cells and CAFs. In addition, the physical force between tumor cells and CAFs promotes cooperative invasion or co-migration of both types of cells. Pro-inflammatory cytokines, such as leukemia inhibitory factor (LIF) and interleukin-6 (IL-6), are secreted by both cancer cells and CAFs, and mediate the epigenetic modification of CAFs. This enhances the pro-tumorigenic function of CAFs mediated by promoting actomyosin contractility and extracellular matrix remodeling to form the tracks used for collective cancer cell migration. The concept of intra-tumoral CAF heterogeneity refers to the presence of inflammatory CAFs with low levels of α-smooth muscle actin (α-SMA) and high levels of IL-6 expression, which are in striking contrast to transforming growth factor-β (TGF-β)-dependent myofibroblastic CAFs with high α-SMA expression levels. CAF populations that suppress tumor growth and progression through stroma-specific Hedgehog (Hh) activation have been detected in different murine tumor models including those of the bladder, colon, and pancreas. A new therapeutic strategy targeting CAFs is the "stromal switch," in which tumor-promoting CAFs are changed into tumor-retarding CAFs with attenuated stromal stiffness. Several molecular mechanisms that can be exploited to design personalized anticancer therapies targeting CAFs remain to be elucidated. Strategies aimed at targeting the tumor stroma as well as tumor cells themselves have attracted academic attention for their application in precision medicine. This novel review discusses the role of the activation of EGFR, Wnt/β-catenin, Hippo, TGF-β, and JAK/STAT cascades in CAFs in relation to the chemoresistance and invasive/metastatic behavior of cancer cells. For instance, although activated EGFR signaling contributes to collective cell migration in cooperation with CAFs, an activated Hippo pathway is responsible for stromal stiffness resulting in the collapse of neoplastic blood vessels. Therefore, identifying the signaling pathways that are activated under specific conditions is crucial for precision medicine.

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“…The characteristic features of the OvCa TME are: (1) resident host cells, in particular huge numbers of activated mesothelial cells which line the peritoneal cavity [ 18 ] and omental adipocytes that constitute the preferred site of OvCa metastasis [ 15 ]; (2) an increased volume of peritoneal fluid in the form of ascites, which generates a rich and intricate microenvironment composed of a network of heterogeneous cell types and tumor-promoting soluble factors, including detached tumor cells [ 67 ], infiltrating immune cells such as T cells [ 68 ] and tumor-associated macrophages (TAMs) [ 69 , 70 ], inflammatory cytokines and growth factors [ 71 ], exosomes [ 72 ] and other host cells. Ascites fluid builds up by malignancy-associated effusion into the peritoneal cavity to facilitate the transcoelomic dissemination of tumor cells to other pelvic and peritoneal organs [ 73 ].…”

Section: The Link Between Obesity and Ovarian Cancermentioning

confidence: 99%

Lipid Regulatory Proteins as Potential Therapeutic Targets for Ovarian Cancer in Obese Women

Yang

Stack

2020

Cancers

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Obesity has become a recognized global epidemic that is associated with numerous comorbidities including type II diabetes, cardiovascular disease, hypertension, and cancer incidence and progression. Ovarian cancer (OvCa) has a unique mechanism of intra-peritoneal metastasis, already present in 80% of women at the time of diagnosis, making it the fifth leading cause of death from gynecological malignancy. Meta-analyses showed that obesity increases the risk of OvCa progression, leads to enhanced overall and organ-specific tumor burden, and adversely effects survival of women with OvCa. Recent data discovered that tumors grown in mice fed on a western diet (40% fat) have elevated lipid levels and a highly increased expression level of sterol regulatory element binding protein 1 (SREBP1). SREBP1 is a master transcription factor that regulates de novo lipogenesis and lipid homeostasis, and induces lipogenic reprogramming of tumor cells. Elevated SREBP1 levels are linked to cancer cell proliferation and metastasis. This review will summarize recent findings to provide a current understanding of lipid regulatory proteins in the ovarian tumor microenvironment with emphasis on SREBP1 expression in the obese host, the role of SREBP1 in cancer progression and metastasis, and potential therapeutic targeting of SREBPs and SREBP-pathway genes in treating cancers, particularly in the context of host obesity.

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Tumor cell‑fibroblast heterotypic aggregates in�malignant ascites of patients with ovarian cancer

Cited by 26 publications

References 36 publications

Exosomes in ovarian cancer ascites promote epithelial–mesenchymal transition of ovarian cancer cells by delivery of miR-6780b-5p

Exosomes in ovarian cancer ascites promote epithelial–mesenchymal transition of ovarian cancer cells by delivery of miR-6780b-5p

Regulation of heterogeneous cancer-associated fibroblasts: the molecular pathology of activated signaling pathways

Lipid Regulatory Proteins as Potential Therapeutic Targets for Ovarian Cancer in Obese Women

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