Collagen-rich omentum is a premetastatic niche for integrin α2-mediated peritoneal metastasis

Huang, Yen‐Lin; Liang, Ching-Yeu; Ritz, Danilo; Coelho, Ruimário Inácio; Septiadi, Dedy; Estermann, Manuela; Cumin, Cécile; Rimmer, Natalie; Schötzau, Andreas; López, Mónica Núñez; Fedier, André; Konantz, Martina; Vlajnic, Tatjana; Calabrese, Diego; Lengerke, Claudia; David, Leonor; Rothen‐Rutishauser, Barbara; Jacob, Francis; Heinzelmann‐Schwarz, Viola

doi:10.7554/elife.59442

Cited by 46 publications

(44 citation statements)

References 65 publications

(82 reference statements)

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“…In a corollary fashion, a ten gene signature that includes collagen-remodeling genes regulated by TGFβ1 signaling has been correlated with increased metastasis and poor patient survival [ 218 ]. This is particularly significant as the omentum is collagen rich and serves as a robust site for tumor cell adhesion via integrins [ 219 ].…”

Section: Tgfβ and Emt In The Metastatic Epithelial Ovarian Cancer Envmentioning

confidence: 99%

TGFβ signaling networks in ovarian cancer progression and plasticity

Asha

Shonibare

Monavarian

et al. 2021

Clin Exp Metastasis

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Epithelial ovarian cancer (EOC) is a leading cause of cancer-related death in women. Late-stage diagnosis with significant tumor burden, accompanied by recurrence and chemotherapy resistance, contributes to this poor prognosis. These morbidities are known to be tied to events associated with epithelial-mesenchymal transition (EMT) in cancer. During EMT, localized tumor cells alter their polarity, cell–cell junctions, cell–matrix interactions, acquire motility and invasiveness and an exaggerated potential for metastatic spread. Key triggers for EMT include the Transforming Growth Factor-β (TGFβ) family of growth factors which are actively produced by a wide array of cell types within a specific tumor and metastatic environment. Although TGFβ can act as either a tumor suppressor or promoter in cancer, TGFβ exhibits its pro-tumorigenic functions at least in part via EMT. TGFβ regulates EMT both at the transcriptional and post-transcriptional levels as outlined here. Despite recent advances in TGFβ based therapeutics, limited progress has been seen for ovarian cancers that are in much need of new therapeutic strategies. Here, we summarize and discuss several recent insights into the underlying signaling mechanisms of the TGFβ isoforms in EMT in the unique metastatic environment of EOCs and the current therapeutic interventions that may be relevant.

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Section: Tgfβ and Emt In The Metastatic Epithelial Ovarian Cancer Envmentioning

confidence: 99%

TGFβ signaling networks in ovarian cancer progression and plasticity

Asha

Shonibare

Monavarian

et al. 2021

Clin Exp Metastasis

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“…reported that integrin alpha 2 (ITGA2), upregulated in omental metastases of patients with ovarian cancer, can trigger tumor cell adhesion to collagen, and then facilitates the migration and peritoneal metastasis of tumor cells. The speculated mechanism of which is that ITGA2 activates the phosphorylation of focal adhesion kinase and the mitogen-activated protein kinase pathway ( 138 ). In another study, lncRNA CASC9 (cancer susceptibility 9) was revealed to be associated with the prognosis and metastasis of esophageal squamous cell carcinoma (ESCC).…”

Section: Resultsmentioning

confidence: 99%

Long Noncoding RNAs in the Metastasis of Oral Squamous Cell Carcinoma

Jiang²,

Shao³

et al. 2021

Front. Oncol.

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Oral squamous cell carcinoma (OSCC) is a common malignant tumor worldwide. Metastasis is the main cause of the death of OSCC patients. Long noncoding RNAs (lncRNAs), one of the key factors affecting OSCC metastasis, are a subtype of RNA with a length of more than 200 nucleotides that has little or no coding potential. In recent years, the important role played by lncRNAs in biological processes, such as chromatin modification, transcription regulation, RNA stability regulation, and mRNA translation, has been gradually revealed. More and more studies have shown that lncRNAs can regulate the metastasis of various tumors including OSCC at epigenetic, transcriptional, and post-transcriptional levels. In this review, we mainly discussed the role and possible mechanisms of lncRNAs in OSCC metastasis. Most lncRNAs act as oncogenes and only a few lncRNAs have been shown to inhibit OSCC metastasis. Besides, we briefly introduced the research status of cancer-associated fibroblasts-related lncRNAs in OSCC metastasis. Finally, we discussed the research prospects of lncRNAs-mediated crosstalk between OSCC cells and the tumor microenvironment in OSCC metastasis, especially the potential research value of exosomes and lymphangiogenesis. In general, lncRNAs are expected to be used for screening, treatment, and prognosis monitoring of OSCC metastasis, but more work is still required to better understand the biological function of lncRNAs.

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“…The extracellular matrix (ECM) is a key component of the TME, and undergoes remodeling during many of the stages of metastasis establishment (63)(64)(65). This remodeling plays a key role particularly in the development and progression of many epithelial cancers including ovarian cancer (33,34,(66)(67)(68). Our 10-gene signature, which overlaps with the signature elucidated by Cheon et al, was thus focused on collagen remodeling genes that are implicated in invasion and metastases in cancer (34,67,68).…”

Section: Discussionmentioning

confidence: 98%

Extracellular vesicle molecular signatures characterize metastatic dynamicity in ovarian cancer

Gonda

Zhao

Shah

et al. 2021

Preprint

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Late-stage diagnosis of ovarian cancer drastically lowers 5-year survival rate from 90% to 30%. Early screening tools that use non-invasive sampling methods combined with high specificity and sensitivity can significantly increase survival. Emerging research employing blood-based screening tools have shown promise in non-invasive detection of cancer. Our findings in this study show the potential of a small extracellular vesicle (sEV)-derived signature as a non-invasive longitudinal screening tool in ovarian cancer. We identified a 7-gene panel in these sEVs that overlapped with an established tissue-derived metastatic ovarian carcinoma signature. We found the 7-gene panel to be differentially expressed with tumor development and metastatic spread. While there were quantifiable changes in genes from the 7-gene panel in plasma-derived sEVs from ovarian cancer patients, we were unable to establish a definitive signature due to low sample number. The most notable finding was a significant change in the ascites-derived sEV gene signature that overlapped with that of the plasma-derived sEV signature at varying stages of disease progression. Taken together our findings show that differential expression of metastatic genes derived from circulating sEVs present a minimally invasive screening tool for ovarian cancer detection and longitudinal monitoring of molecular changes associated with progression and metastatic spread.

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Collagen-rich omentum is a premetastatic niche for integrin α2-mediated peritoneal metastasis

Cited by 46 publications

References 65 publications

TGFβ signaling networks in ovarian cancer progression and plasticity

TGFβ signaling networks in ovarian cancer progression and plasticity

Long Noncoding RNAs in the Metastasis of Oral Squamous Cell Carcinoma

Extracellular vesicle molecular signatures characterize metastatic dynamicity in ovarian cancer

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