Exosomes released from cisplatin-resistant ovarian cancer cells modulate the reprogramming of cells in tumor microenvironments toward the cancerous cells

Yılmaz, Gizem; Tavsan, Zehra; Cagatay, Elcin; Kursunluoglu, Gizem; Kayalı, Hülya Ayar

doi:10.1016/j.biopha.2022.113973

Cited by 10 publications

(3 citation statements)

References 57 publications

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“…Ovarian cancer exosomes carry a substantial amount of DNA, RNA, proteins, and other biomacromolecules. , Compared with other exosomal cargoes, exosomal proteins can provide abundant, stable, sensitive, and unique information. , Representative proteins in ovarian cancer exosomes include EpCAM, CD24, CA125, etc. − There are significant differences in the protein profile expression of exosomes from various cancer types, suggesting that these proteins are implicated in cancer development and type (Figure a). Moreover, exosomes exhibit significant advantages in reflecting patient-specific differences and detecting dynamic cancer progression.…”

Section: Results and Discussionmentioning

confidence: 99%

Dual-Aptamer Recognition of DNA Logic Gate Sensor-Based Specific Exosomal Proteins for Ovarian Cancer Diagnosis

Zhao,

Li,

Zhao

et al. 2024

ACS Sens.

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Clinical diagnosis of ovarian cancer lacks high accuracy due to the weak selection of specific biomarkers along with the circumstance biomarkers localization. Clustering analysis of proteins transported on exosomes enables a more precise screening of effective biomarkers. Herein, through bioinformatics analysis of ovarian cancer and exosome proteomes, two coexpressed proteins, EpCAM and CD24, specifically enriched, were identified, together with the development of an as-derived dualaptamer targeted exosome-based strategy for ovarian cancer screening. In brief, a DNA ternary polymer with aptamers targeting EpCAM and CD24 was designed to present a logic gate reaction upon recognizing ovarian cancer exosomes, triggering a rolling circle amplification chemiluminescent signal. A dynamic detection range of 6 orders of magnitude was achieved by quantifying exosomes. Moreover, for clinical samples, this strategy could accurately differentiate exosomes from healthy persons, other cancer patients, and ovarian cancer patients, enabling promising in situ detection. By accurately selecting biomarkers and constructing a dual-targeted exosomal protein detection strategy, the limitation of insufficient specificity of traditional protein markers was circumvented. This work contributed to the development of exosome-based prognosis monitoring in ovarian cancer through the identification of disease-specific exosome protein markers.

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Section: Results and Discussionmentioning

confidence: 99%

Dual-Aptamer Recognition of DNA Logic Gate Sensor-Based Specific Exosomal Proteins for Ovarian Cancer Diagnosis

Zhao,

Li,

Zhao

et al. 2024

ACS Sens.

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“…19 Furthermore, extracellular vesicles (or exosomes) released by OC cells have the ability to disseminate to the abdominal cavity, fostering gastrointestinal metastasis. 20 Alterations in the tumor microenvironment, encompassing factors such as estrogen, exosomes, and MUC4, are likely to be influential contributors to the metastatic process of OC.…”

Section: Discussionmentioning

confidence: 99%

Ovarian serous carcinoma with stomach metastasis: a rare case report and literature review

Hu,

Guo,

Wang

et al. 2024

J Int Med Res

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Ovarian cancer is a common tumor among women. It is often asymptomatic in the early stages, with most cases already at stage III to IVE at the time of diagnosis. Direct spread and lymphatic metastasis are the primary modes of metastasis, whereas hematogenous spread is rare. An initial diagnosis of ovarian cancer that has metastasized to the stomach is also uncommon. Therefore, clear treatment methods and prognostic data for such metastasis are lacking. In our hospital, we encountered a patient with an initial imaging diagnosis of a gastric tumor and a history of an ovarian tumor with endoscopic abdominal metastasis. Based on the characteristics of the case, the two tumors were considered to be the same. After chemotherapy, a partial response was observed in the stomach and pelvic lesions, suggesting the effectiveness of the treatment. Through three treatments of recurrence, gastroscopy confirmed the stomach to be a metastatic site. Therefore, determining the primary source of advanced tumors is crucial in guiding treatment decisions. Clinicians must approach this comprehensively, relying on thorough evaluation and personal experience.

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“…Among them, there is the sustained secretion within TME of EVs with an altered molecular cargo, which regulates the heterogeneous cellular populations within TME. In line with this, during exposure to CDDP, tumor cells secrete EVs that affect the sensitivity of the surrounding cells [57]. In addition, CDDP was demonstrated to induce a minor secretion of EVs in ovarian cancer cell lines [48,58], but with different molecular cargo and biological functions [58].…”

Section: Discussionmentioning

confidence: 99%

Intraluminal vesicle trafficking is involved in the secretion of base excision repair protein APE1

Parolini,

Degrassi,

Spadaro

et al. 2024

The FEBS Journal

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The apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is an essential enzyme of the base excision repair pathway of non‐distorting DNA lesions. In response to genotoxic treatments, APE1 is highly secreted (sAPE1) in association with small‐extracellular vesicles (EVs). Interestingly, its presence in the serum of patients with hepatocellular or non‐small‐cell‐lung cancers may represent a prognostic biomarker. The mechanism driving APE1 to associate with EVs is unknown, but is of paramount importance in better understanding the biological roles of sAPE1. Because APE1 lacks an endoplasmic reticulum‐targeting signal peptide, it can be secreted through an unconventional protein secretion endoplasmic reticulum–Golgi‐independent pathway, which includes an endosome‐based secretion of intraluminal vesicles, mediated by multivesicular bodies (MVBs). Using HeLa and A549 cell lines, we investigated the role of endosomal sorting complex required for transport protein pathways (either‐dependent or ‐independent) in the constitutive or trichostatin A‐induced secretion of sAPE1, by means of manumycin A and GW 4869 treatments. Through an in‐depth biochemical analysis of late‐endosomes (LEs) and early‐endosomes (EEs), we observed that the distribution of APE1 on density gradient corresponded to that of LE–CD63, LE–Rab7, EE–EEA1 and EE–Rab 5. Interestingly, the secretion of sAPE1, induced by cisplatin genotoxic stress, involved an autophagy‐based unconventional secretion requiring MVBs. The present study enlightens the central role played by MVBs in the secretion of sAPE1 under various stimuli, and offers new perspectives in understanding the biological relevance of sAPE1 in cancer cells.

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Exosomes released from cisplatin-resistant ovarian cancer cells modulate the reprogramming of cells in tumor microenvironments toward the cancerous cells

Cited by 10 publications

References 57 publications

Dual-Aptamer Recognition of DNA Logic Gate Sensor-Based Specific Exosomal Proteins for Ovarian Cancer Diagnosis

Dual-Aptamer Recognition of DNA Logic Gate Sensor-Based Specific Exosomal Proteins for Ovarian Cancer Diagnosis

Ovarian serous carcinoma with stomach metastasis: a rare case report and literature review

Intraluminal vesicle trafficking is involved in the secretion of base excision repair protein APE1

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